Changes in serum free testosterone, sleep patterns, and 5-alpha-reductase type I activity influence changes in sebum excretion in female subjects.

BACKGROUND/PURPOSE: Sebum is thought to play an important role in acne vulgaris and sebum excretion rate (SER) is often used as a marker of efficacy in acne studies. This study explored factors that could induce intra-subject variability in SER. METHODS: SER was measured twice, 7 days apart, on the forehead of 40 healthy subjects. At each visit, the following parameters were also evaluated: serum androgen levels, 5-alpha-reductase type I gene expression, forehead temperature, sleep habits, diet, facial washing routine, and UV exposure. RESULTS: There was a positive correlation between the time subjects fell asleep on Day 0 and the change in SER for the left (P = 0.010; R = 0.402) and right sides (P = 0.002; R = 0.467) of the forehead. There was a significant inverse correlation between SER and 5-alpha-reductase type 1 expression and between free testosterone levels and 5-alpha-reductase type 1 expression. In sub-analyses performed on men and women, these correlations were only significant for women. CONCLUSION: Variations in sleep patterns, free testosterone, and 5-alpha-reductase type 1 activity are associated with changes in sebum excretion in women. This could explain some of the inter-subject variability in SER measured between visits in clinical studies.

Allergy to dust mites may contribute to early onset and severity of alopecia areata.

BACKGROUND: A higher risk of allergic diseases such as rhinitis, asthma and atopic eczema (atopic dermatitis) has been reported for patients with alopecia areata (AA) compared with the general population, but the significance of this is still largely unclear. AIM: To determine whether serum total or specific IgE play a role in the onset and severity of AA. METHODS: We tested 461 serum samples from 351 patients with AA and 110 healthy controls (HC) for total IgE (tIgE) and specific IgE (sIgE) by ImmunoCAP-100 or in vitro test (IVT). RESULTS: The absolute value of tIgE was higher in patients with AA than in normal controls (P < 0.001), although the prevalence of raised tIgE (> 120 IU/mL) detected in patients with AA (29.3%) was similar to that of HC (21.8%). Prevalences of raised sIgE against various allergens detected by ImmunoCAP-100 showed that Dermatophagoides pteronyssinus (Der p; 31.1%) and Dermatophagoides farinae (Der f; 29.0%) were the most common allergens. Similar results were found by IVT, with the most common response being against Der p/Der f (29.0%). However, the prevalences of tIgE and sIgE against dust mites (Der p and Der f) in patients with early-onset AA and severe AA were significantly higher than those with late-onset AA and mild AA (P = 0.02, P = 0.02 vs. P = 0.03 and P = 0.001, respectively). Notably, the increases in tIgE and sIgE were independent of atopy history. CONCLUSIONS: Allergy to dust mites may have an effect on the immune response in AA, and may contribute to its early onset and severity in patients of Chinese origin.

Non-scarring patchy alopecia in patients with systemic lupus erythematosus differs from that of alopecia areata.

BACKGROUND: Non-scaring patchy alopecia associated with systematic lupus erythematosus (SLE) is sometimes mis-diagnosed as alopecia areata (AA). OBJECTIVES: Our aim was to differentiate non-scarring patchy SLE alopecia features from patchy AA. METHODS: Clinical, dermatoscopic and histopathological data from 21 SLE patients with patchy alopecia were compared with data from 21 patients with patchy AA. RESULTS: Incomplete alopecia was common in SLE alopecia patches, while AA patches exhibited complete alopecia. Exclamation-mark hairs, black dots, broken hair and yellow dots were common to AA, while hair shaft thinning and hypopigmentation, angiotelectasis, peripilar sign, perifollicular red dots, white dots and honeycomb pigment patterns were more common in SLE. Interfollicular polymorphous vessels were the most common angiotelectasis presentation in the SLE alopecia patches, but interfollicular arborizing vessels were significantly more common in non-hair-loss-affected SLE regions and in AA hair-loss regions. During follow-up, increased vellus hair was the earliest feature that emerged after treatment both in SLE and AA, while the earliest feature that disappeared was hair shaft hypopigmentation in SLE and broken hair in AA. After treatment, no SLE patients had relapse of alopecia, while 41.7% of AA patients did. CONCLUSION: Distinct clinical, dermatoscopic and histopathological features were found in SLE-associated alopecia regions, which were different from those of AA. Serological autoantibody tests are of value to confirm the differential diagnosis. Local angiotelectasis and vasculitis close to hair follicles may be involved in the pathogenesis of alopecia in SLE.

What causes alopecia areata?

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8(+) T cells, CD4(+) T cells and NKGD2(+) NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA-related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re-evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease.

Promising therapies for treating and/or preventing androgenic alopecia.

Androgenetic alopecia (AGA) may affect up to 70% of men and 40% of women at some point in their lifetime. While men typically present with a distinctive alopecia pattern involving hairline recession and vertex balding, women normally exhibit a diffuse hair thinning over the top of their scalps. The treatment standard in dermatology clinics continues to be minoxidil and finasteride with hair transplantation as a surgical option. Here we briefly review current therapeutic options and treatments under active investigation. Dutasteride and ketoconazole are also employed for AGA, while prostaglandin analogues latanoprost and bimatoprost are being investigated for their hair growth promoting potential. Laser treatment products available for home use and from cosmetic clinics are becoming popular. In the future, new cell mediated treatment approaches may be available for AGA. While there are a number of potential treatment options, good clinical trial data proving hair growth efficacy is limited.

CXCR3 ligands promote expression of functional indoleamine 2,3-dioxygenase in basal cell carcinoma keratinocytes.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in humans worldwide. Studies suggest that BCCs exhibit immunoprotection, similar to other keratinocyte carcinomas, although the mechanisms of defence have not been defined. OBJECTIVES: To examine if indoleamine 2,3-dioxygenase (IDO), an immune privilege-associated enzyme, would be expressed in BCC, regulated in part by CXCR3. METHODS: We analysed the expression and function of IDO in human BCC (hBCC) tissues using nonlesional skin epithelial (NL) tissues as a control. RESULTS: Quantitative real-time reverse transcription-polymerase chain reaction (qPCR) revealed significant upregulation of IDO1 and IDO2 (12·5- and 19·14-fold change, respectively) in nodular hBCCs as compared with NL tissues. Immunohistochemistry showed that IDO colocalized with keratin 17, a BCC keratinocyte marker, in hBCC tissues. Western blot identified a full-length IDO (42 kDa) product and a splice variant (∼30 kDa) in BCC tissues. Kynurenine assays and qPCR were conducted to determine IDO enzymatic activity in hBCCs in vitro with CXCL11 supplementation, which has previously been shown to be required for the tumour cell growth. Addition of CXCL11 upregulated IDO2 and increased l-kynurenine concentration in a dose-dependent manner in hBCCs while normal primary keratinocytes exhibited no response. CONCLUSIONS: The expression of IDO at both mRNA and protein levels in hBCC tissues, the upregulation of IDO2 and the IDO-mediated l-kynurenine production in hBCCs with CXCL11 treatment suggest that functional IDO is synthesized by hBCC tumours and may be used as a method of immunoprotection during tumorigenesis. Also, IDO enzymatic activity may be modulated by CXCR3/CXCL11 signalling in BCCs.

Interferon-gamma-deficient mice are resistant to the development of alopecia areata.

BACKGROUND: Alopecia areata (AA) is a T-cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4(+) T cells. However, whether T-helper (Th) 1 or Th2 cytokines are predominant has not yet been defined. OBJECTIVES: To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)-gamma in the experimental induction of AA. METHODS: AA was experimentally induced by grafting full-thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN-gamma gene (IFNgamma(-/-)) and on to wild-type mice (IFNgamma(+/+)). RESULTS: While 90% of wild-type mice developed AA, none of the IFNgamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4(+) and CD8(+) T cells in controls, while in IFNgamma(-/-) mice skin-infiltrating CD8(+) T cells were absent and the number of CD4(+) cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune-privileged infrainfundibular site of the hair follicle was found to be weaker in AA-resistant IFNgamma(-/-) mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFNgamma(-/-) mice did not respond to the transfer of AA-affected skin. As distinct from IFNgamma(+/+) mice, neither T-cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin-infiltrating leucocytes of AA-resistant IFNgamma(-/-) mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFNgamma(-/-) mice. CONCLUSIONS: IFNgamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA.

Insulin pump therapy in children and adolescents: improvements in key parameters of diabetes management including quality of life.

AIMS: To determine the impact of insulin pump therapy (continuous subcutaneous insulin infusion) on key parameters of diabetes management including quality of life in children and adolescents with Type 1 diabetes mellitus (T1DM). METHODS: All patients started on insulin pump therapy were prospectively followed before and after institution of insulin pump therapy. Data collected included age, duration of diabetes, glycated haemoglobin levels (HbA1c), anthropometric data and episodes of severe hypoglycaemia defined as hypoglycaemia resulting in coma or convulsion. A subset of patients also completed the Diabetes Quality of Life Instrument (DQOL) and Self-Efficacy for Diabetes Scale (SED) questionnaires to assess quality of life. RESULTS: At the time of analysis, 100 patients had been managed with insulin pump therapy. The mean age when starting pump therapy was 12.5 (3.9-19.6) years. Duration of therapy ranged from 0.2 to 4.0 years (mean 1.4 years, median 1.5 years). HbA1c decreased from 8.3 +/- 0.1% prior to pump therapy to 7.8 +/- 0.1% (P < 0.0001). Episodes of severe hypoglycaemia decreased from 32.9 to 11.4 per 100 patient years. Components of quality of life measures showed improvement on pump treatment. BMI standard deviation scores (z scores) did not increase. CONCLUSIONS: Pump therapy is proving an effective means of insulin therapy in the young patient that shows promise to improve glycaemic control with a reduction in hypoglycaemia frequency. Quality of Life measures suggest that psychosocial outcomes may be improved.

Treatment of alopecia areata in the DEBR model using Cyclosporin A lipid vesicles.

Alopecia areata (AA) is a chronic cutaneous disease with a suspected autoimmune origin. We evaluated the efficacy of 0.5% Cyclosporin A (CyA) in a topically applied liposomal formulation as a potential treatment for AA using the Dundee Experimental Bald Rat (DEBR) model. The vehicle consisted of liposomes (75% phosphatidylcholine, 5% lysophosphatidylcholine, 5% sterol, natural oils) of 10% wt. in ethanol with and without 2% wt. terpenes (d-limonene: citral: cineole, 10:45:45) as a penetration enhancer (PE). Fifteen DEBR were allocated to 3 groups of 5. Groups I, II and III received CyA vesicles with PE, CyA vesicles without PE, and CyA in ethanol respectively. All rats were treated twice a day for 6 weeks within a 4 cm2 area on one bald flank with CyA while the contralateral flank received an equivalent control formulation. Rats in group I exhibited visible hair regrowth on the drug treated site after one week of drug application. Group II rats had visible hair regrowth by the end of the second week. The hair growth was progressive and reached a maximum density at the site of application after six weeks in both groups. Histological examination revealed a reduced inflammatory infiltrate and improved hair follicle morphology within the drug treated area as compared to the contralateral vehicle treated skin. Group III rats showed neither visible signs of hair growth nor reduction of hair follicle inflammation. The results of this proof of concept preliminary study suggest that CyA vesicle formulations with and without PE have promising potential as a topical treatment for AA in humans.

Chronic delayed-type hypersensitivity reaction as a means to treat alopecia areata.

The acute phase of alopecia areata (AA) is characterized by an increase in CD44v3+ and CD44v10+ skin-infiltrating leucocytes (SkIL). Induction of a contact eczema, one of the therapeutic options in AA, can be mitigated strongly by a blockade of CD44v10. The observation that induction of a delayed type hypersensitivity (DTH) reaction abrogates an autoimmune reaction, where both responses apparently use similar effector mechanisms, is surprising and prompted us to search for the underlying mechanisms. AA-affected C3H/HeJ mice were treated with the contact sensitizer SADBE (squaric acid dibutylester) and leucocyte subpopulations and their activation state was evaluated in SkIL and draining lymph nodes. AA-affected mice exhibited an increased number of SkIL with a predominance of T lymphocytes. After treatment with the contact sensitizer SADBE recovery of SkIL was reduced and monocytes predominated. However, a significantly increased number of leucocytes was recovered from draining lymph nodes. Draining lymph node cells from untreated and treated AA mice exhibited all signs of recent activation with high-level expression of co-stimulatory and accessory molecules and an increased percentage of CD44v3+ and CD44v10+ leucocytes. In contrast, SkIL of SADBE-treated AA mice contained relatively few activated T cells and reduced numbers of CD44v3+ and CD44v10+ cells. Thus, the activation state and the distribution of leucocyte subsets in SADBE-treated AA mice are consistent with a blockade of leucocyte extravasation. Accordingly, the therapeutic effect of long-term SADBE treatment may rely on impaired leucocyte traffic.

Alopecia areata in C3H/HeJ mice involves leukocyte-mediated root sheath disruption in advance of overt hair loss.

Alopecia areata (AA) can be induced in C3H/HeJ mice by grafting full-thickness AA-affected skin. An 8- to 12-week delay between surgery and overt hair loss onset provides an opportunity to examine disease pathogenesis. Normal haired C3H/HeJ mice were sham-grafted or grafted with AA-affected skin. Mice were euthanatized 2, 4, 6, 8, 10, and 12 weeks after surgery along with chronic AA-affected mice as a positive control. Until 6 weeks after grafting, inflammation was only evident around anagen-stage hair follicles in host skin adjacent to but not distant from the AA-affected graft. From 8 weeks on, AA-grafted but not sham-grafted mice exhibited a diffuse dermal inflammation at distant sites that progressively focused on anagen-stage hair follicles at 10 and 12 weeks. Perifollicular inflammation was primarily composed of CD4+ and CD8+ cells associated with follicular epithelium intercellular adhesion molecule -1 expression. Only CD8+ cells penetrated intrafollicularly by 12 weeks after surgery, although both CD4+ and CD8+ intrafollicular cells were observed in chronic AA-affected mice. Under electron microscopy, intrafollicular lymphocyte and macrophage infiltration associated with hair follicle dystrophy was prominent 10 weeks after surgery, primarily within the differentiating outer and inner root sheaths. This study shows that focal follicular inflammation develops some time in advance of overt hair loss and focuses on the differentiating root sheaths in C3H/HeJ mice. The severity of inflammation and the degree of hair follicle dystrophy induced by the infiltrate appear to reach a threshold level before overt hair loss occurs.

Dietary soy oil content and soy-derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/HeJ mice.

Alopecia areata (AA) is a complex, multi-factorial disease where genes and the environment may affect susceptibility and severity. Diet is an environmental factor with the potential to influence disease susceptibility. We considered dietary soy (soya) oil content and the soy-derived phytoestrogen genistein as potential modifying agents for C3H/HeJ mouse AA. Normal haired C3H/HeJ mice were grafted with skin from spontaneous AA affected mice, a method previously shown to induce AA. Grafted mice were given one of three diets containing 1%, 5% or 20% soy oil and observed for AA development. In a separate study, mice on a 1% soy oil diet were injected with 1 mg of genistein three times per week for 10 weeks or received the vehicle as a control. Of mice on 1%, 5%, and 20% soy oil diets, 43 of 50 mice (86%), 11 of 28 mice (39%), and 2 of 11 mice (18%) developed AA, respectively. Four of 10 mice injected with genistein and 9 of 10 controls developed AA. Mice with AA had hair follicle inflammation consistent with observations for spontaneous mouse AA, but no significant association was observed between the extent of hair loss and diet or genistein injection. Mice that failed to develop AA typically experience white hair regrowth from their skin grafts associated with a moderate macrophage and dendritic cell infiltration. Soy oil and derivatives have previously been reported to modify inflammatory conditions. Hypothetically, soy oil compounds may act on C3H/HeJ mice through modulating estrogen-dependent mechanisms and/or inflammatory activity to modify AA susceptibility.

Alopecia areata - animal models.

Several rodent models with spontaneous and induced alopecia areata (AA), a nonscarring inflammatory hair loss disease with suspected autoimmune elements, have been identified. Of these, the C3H/HeJ mouse and DEBR rat have been most extensively used in examining AA development. Flow cytometry and micro array characterization, manipulation of inflammatory cells by in vivo cell depletion or cell receptor blockade, lymph node cell transfer between affected and unaffected rodents, and the recent use of transgenic knockout mice have given important insights into the development of AA. From our current understanding of rodent models, the development of AA relies upon a general genetic susceptibility where major susceptibility genes may be supplemented by minor disease severity modifying genes. However, the actual onset of AA, its duration, extent, and persistence in individual rodents may be modified by epigenetic factors. Rodent AA seems to be fundamentally, but not exclusively, Th1 cell mediated. Onset of disease may be dependent on several factors including the break down of the putative anagen stage hair follicle immune privilege, appropriate antigen presentation with costimulation of lymphocytes, presence of autoreactive lymphocytes, and a deficiency of functional immune system regulatory cells. Rodents have already been used in examining a variety of current AA treatments and developing new therapies with some success. With a greater understanding of AA disease mechanisms through rodent model research, improved and more specific treatment interventions may be defined.

Melanocyte and gonad activity as potential severity modifying factors in C3H/HeJ mouse alopecia areata.

Circumstantial evidence has previously suggested gonad derived steroid hormones and melanogenesis related antigens may modify human alopecia areata (AA). AA-like hair loss can be induced in C3H/HeJ mice after skin allografts from spontaneous AA-affected mice. This inducible model was used to evaluate hormones and hair follicle melanocyte presence as disease-severity modifiers. Ten females and 9 males were gonadectomized and received AA-affected allografts. All gonadectomized mice had 2-4 weeks delay in AA onset relative to non-gonadectomized controls. Two females and 4 males failed to develop any AA by 25 weeks after grafting. The experiment was repeated with gonadectomized female and male mice plus non-gonadectomized mice subcutaneously implanted with silastic capsules containing 80 microg 17beta estradiol or 10 mg 5alpha dihydrotestosterone, respectively. Five of 11 ovariectomized and 9 of 11 non-ovariectomized, estradiol supplemented females developed AA with extremely rapid progression. Three of 8 castrated, but none of 11 non-castrated, dihydrotestosterone-supplemented males expressed AA. In a separate study, 14 mice were freeze-branded, producing white hair on the dorsal lumbar region, and later received full-thickness allografts. Thirteen mice developed patchy pigmented and non-pigmented hair loss. One mouse developed diffuse, pigmented hair loss, but with white hair survival persisting 25 weeks after grafting. The results suggest that gonadal steroid hormones can modulate C3H/HeJ mouse AA where estradiol promoted rapid progression of AA while dihydrotestosterone increased resistance to AA onset. In general, both pigmented and non-pigmented C3H/HeJ mouse hair is susceptible to AA. Murine AA susceptibility and severity clearly involves an interplay between genetic and epigenetic factors.

Treatment of alopecia areata in C3H/HeJ mice with the topical immunosuppressant FK506 (Tacrolimus).

Alopecia areata-like hair loss has been observed in C3H/HeJ mice and can be defined as a tissue-restricted T cell mediated disease of the hair follicle. Because FK506 has been described as suppressing T cell mediated autoimmune diseases, we addressed the question whether topical treatment of C3H/HeJ mice with FK506 has a beneficial effect on alopecia areata (AA). For this purpose six C3H/HeJ mice with AA were treated topically with 0.1% FK506 ointment, four mice received the vehicle only. Four of six FK506-treated mice showed complete hair regrowth, whereas 1/4 vehicle-treated mice regrew hair. Mice treated successfully with FK506 had reduced perifollicular infiltrates of CD4+ and CD8+ cells and a decreased expression of MHC class I and II and ICAM-1 on hair follicle epithelium, compared to control mice. We conclude that topical treatment with FK506 is able to induce hair regrowth in AA of C3H/HeJ mice, most likely by suppressing the T cell mediated immune response.

Current and potential agents for the treatment of alopecia areata.

Alopecia areata is considered to be a T-cell mediated autoimmune disease of the hair follicle. Current immunosuppressive approaches and immunomodulatory treatment with contact sensitizers such as diphenylcyclopropenone and squaric acid dibutylester are dealt with in this review article. The efficacy of the various modes of treatment is evaluated by a review of literature and their mode of action is discussed. In accordance with the mechanism of autoimmune pathogenesis of AA, improved future treatments may be immunosuppressive or immunomodulatory, or they should otherwise protect the hair follicle from the injurious effects of the inflammation. Such possible future therapeutic approaches include the use of liposomes as an improved vehicle, application of immunosuppressive cytokines like TGF-beta and IL-10, inhibition of apoptosis mediated by the Fas-FasL system, inhibition of the lymphocyte homing receptor CD44v10, induction of tolerance as well as principles of gene therapy.

Alopecia areata: an autoimmune disease?

A wide range of hypotheses such as focal infection, trophoneuroses, and endocrine dysfunction, have been previously proposed to explain the pathogenesis of alopecia areata (AA). Currently, the most widely held belief is that AA is an autoimmune disease with cellular and/or humoral immunity directed against anagen hair follicle antigen(s). However, until recently evidence in support of an autoimmune mechanism of AA has been largely circumstantial. More fundamental evidence has recently been amassed in support of AA as an autoimmune disease by using animal models. These data include: 1) identification of cross-species hair follicle specific IgG autoantibodies, 2) The ability to induce AA in an animal model with transfer of skin from affected to naive individuals, and 3) the induction of disease by transfer of lymphocytes to human skin grafted to severe combined immunodeficiency mutant mice. A review of the previous and current data related to the autoimmune basis of AA is provided to put into perspective the future studies needed to definitively determine whether AA is an autoimmune disease.

Successful treatment of alopecia areata-like hair loss with the contact sensitizer squaric acid dibutylester (SADBE) in C3H/HeJ mice.

A type of hair loss closely resembling human alopecia areata has been described in C3H/HeJ mice. In order to test the assumed analogy with human alopecia areata, we investigated the efficacy of treatment with the contact allergen squaric acid dibutylester. In 12 C3H/HeJ mice with alopecia areata an allergic contact dermatitis was induced and elicited weekly on one side of the back by topical applications of squaric acid dibutylester. Overt hair regrowth was observed only on the treated side of the back in nine of 12 mice. Histopathologic examination revealed a change in the distribution of the inflammatory infiltrate from a dense perifollicular lymphocytic infiltrate around the mid and lower regions of hair follicles in untreated skin to a uniform presence in the upper dermis in treated skin. Immunohistomorphometric studies revealed that treatment with squaric acid dibutylester increased the CD4+/CD8+ ratio from approximately 1:2 in untreated alopecia areata to 1:1 in treated alopecia areata. Additional immunohistochemical investigations showed an aberrant expression of major histocompatibility complex class I, major histocompatibility complex class II and intercellular adhesion molecule 1 on keratinocytes of the mid and lower parts of hair follicles in untreated alopecia areata. In successfully treated skin ectopic major histocompatibility complex class I and II expression was clearly reduced, whereas intercellular adhesion molecule 1 expression showed only minor changes. In conclusion, alopecia areata-like hair loss in C3H/HeJ mice responded to treatment with the contact sensitizer squaric acid dibutylester analogous to human alopecia areata. Moreover, successful treatment changes the aberrant expression of major histocompatibility complex class I and II in a way similar to that observed in human alopecia areata. These observations support the concept that alopecia areata-like hair loss in C3H/HeJ mice can be utilized as an appropriate model for the study of human alopecia areata.