Interleukin-1 receptor antagonist allele 2 and familial alopecia areata

Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair follicle. It is characterized by loss of hair in patches (alopecia areata) with progression in some individuals to total loss of scalp hair (alopecia totalis) or to loss of all scalp and body hair (alopecia universalis). The interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with more severe clinical outcome in several chronic inflammatory diseases, including alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia areata severity in a British case-control study. In this paper, we analyzed alopecia areata probands in a family-based sample (n = 131 parent-offspring trios) to study the association between alleles of the IL-1RN and various phenotypes of alopecia areata. In considering all patients with any form of alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not associated with alopecia totalis and alopecia universalis. A borderline association was observed between IL-1RN and patchy alopecia areata but it was not statistically significant (p =0.06). We also observed an association between IL1-RN*1 allele and patchy alopecia areata (p =0.045).     

The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis

Many diseases, notably those having a strong autoimmune component, have been shown to have an association with specific human leukocyte antigens (HLA). The molecular basis for this genetic association with disease is the fact that HLA bind and present peptides derived from self and foreign protein antigens to the immune system for recognition and activation of the immune response. Previous studies with heterogeneous groups of alopecia areata (AA) patients have suggested associations with some HLA class I and class II antigens. For this study we selected only patients with long-standing disease and stratified them into two groups by strict definitions of duration and extent of disease: those with patchy AA and those with either alopecia totalis (AT) or alopecia universalis (AU). The patients were tissue typed for HLA class II antigens by biomolecular methods that provided antigen discrimination at an allele level. More than 80% of all of the AA patients typed were positive for the antigen DQB1*03 (DQ3), suggesting that this antigen is a marker for general susceptibility to AA. In addition, two other antigens were found significantly increased in frequency only in the group of AT/AU patients, DRB1*0401 (DR4) and DQB1*0301(DQ7). This strongly suggests that the two clinical types of AA, namely patchy AA versus AT/AU, can be distinguished by a genetically based predisposition to extent of disease.     

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.     

Mycosis fungoides: HLA class II associations among Ashkenazi and non-Ashkenazi Jewish patients

BACKGROUND: An immunogenetic mechanism has been suggested to play a role in the pathogenesis of mycosis fungoides (MF). While results of studies on HLA class I associations haveproved inconsistent, two previous studies showed that certain HLA class II alleles were significantly increased among North American caucasian patients with MF: HLA-DRB1*11 and DQB1*03. OBJECTIVES: To investigate the possible HLA class I and class II associations with MF among Jewish patients. METHODS: The patient group comprised 68 Jewish patients with MF: 38 Ashkenazi and 30 non-Ashkenazi. The control group comprised 252 healthy Jewish volunteers: 132 Ashkenazi and 120 non-Ashkenazi. Tissue typing for HLA class I (A and B) was performed using the National Institutes of Health microlymphocytotoxicity technique. DNA-based low-medium resolution analysis for DRB1* and DQB1* alleles was performed using polymerase chain reaction (PCR) amplification with sequence-specific primers. For those alleles found to have significantly increased frequency, high-resolution analysis was done by means of PCR sequence-specific oligotyping. RESULTS: The allele frequency of HLA-DRB1*11 was found to be significantly increased but only among Ashkenazi patients with MF (30% vs. 19% in the controls; P = 0.034). High-resolution analysis for DRB1*11, not previously performed, suggested that its greater frequency is due to the increased number of Ashkenazi MF patients with the DRB1*1104 allele (P corrected = 0.036). Analysed together, DQB1*03 alleles (DQB1*0301-0304) had a significantly greater frequency in MF as a group as compared with controls (47% vs. 33%, P = 0.003). DQB1*0301 was demonstrated to be the specific allele associated with MF in Jewish patients (allele frequency of 36% vs. 23% in controls; P corrected = 0.0068), which was not the case for North American caucasian patients with MF. No greater frequencies of any of the HLA class I A or B antigens were found. CONCLUSIONS: Our findings further demonstrate the 'universality' of MF HLA class II susceptibility alleles, i.e. HLA-DRB1*11 and HLA-DQB1*03, suggesting that HLA polymorphism is likely to be important in the pathogenesis of MF in Jewish patients, as it is in North American caucasian patients. Not previously reported is our finding that HLA-DRB1*1104 is the specific allele more prevalent among patients with MF. Our study also underscores some differences in HLA profiles between non-Jewish and Jewish patients with MF and between Ashkenazi and non-Ashkenazi Jewish patients, indicating the possibility of diverse HLA disease associations in populations with different genetic backgrounds. Our study provides further evidence for the lack of association between HLA class I and MF.     

Alopecia areata in families: association with the HLA locus

Alopecia areata (AA) is a T cell mediated disease directed against hair follicles that results in bald patches. It can range in severity from patchy (AA), to total scalp hair loss (alopecia totalis; AT) or body hair loss (alopecia universalis; AU). We have previously shown that HLA-DR4 and DR11 as well as HLA-DQ*03 alleles are increased in unrelated AA patients compared with controls. To study whether class II HLA alleles are linked to AA, we investigated 81 extended families that included 192 AA patients, including 89 with AT or AU. We also performed the transmission disequilibrium test (TDT) in 143 nuclear families. Results showed an association between alleles of HLA-DQB (p = 0.014) and HLA-DR (p = 0.010). We also performed linkage analysis in 75 families whose members' genomic DNA were available for HLA typing. Results from this analysis support linkage between AA and class II loci with a maximal LOD score of 2.42 to HLA-DQB at 5% recombination, and with a maximal LOD score of 2.34 to HLA-DR at 0% recombination. There was an increased incidence of atopic dermatitis and autoimmune thyroiditis in families. AA appears to be a class II HLA restricted organ specific immune response to the hair follicle.     

Association between psoriasis vulgaris and MHC-DRB, -DQB genes as a contribution to disease diagnosis

We analyzed 100 control individuals and 60 patients with psoriasis vulgaris from the population of Campinas, Brazil. Typification of class II HLA alleles (HLA-DRB1-5 and -DQB1) was carried out through the DNA/PCR/SSP at medium and high resolution. DNA was extracted through a salting-out procedure: 13 DRB1 alleles, 3 DRB3 alleles, 1 DRB4 allele, 2 DRB5 alleles, and 5 DQB1 alleles were identified at a medium resolution using the PCR/SSP, and 45 DRB1 alleles were identified at a high resolution in analyzed patients. Results showed associations with psoriasis vulgaris: positive associations HLA-DRB3*02 (p < 0.05, chi(2) = 5.10, RR = 2.14); HLA-DRB1*0102 alleles (p < 0.05, RR = 5.44). Negative associations were found for HLA-DRB4*01 (chi(2) = 3.23, RR = 0.55) and HLA-DRB1*1302 alleles (p < 0.05, RR = 0.23). The haplotypes revealed positive association for HLA-DRB1*0102/DQB1*05 (p < 0.05, RR = 5.44) and HLA-DRB1*0701/DQB1*03 alleles (p < 0.02, RR = 9.00). These findings suggest a possible association of the DRB1 allele with the group of patients showing an early onset of the illness, as well as an association with haplotypes HLA-DRB1*0102/DQB1*05 and HLA-DRB1*0701/DQB1*03.     

HLA in alopecia areata

BACKGROUND: The aim of this study was to investigate the human leukocyte antigen (HLA) characteristics of Turkish alopecia areata patients, and the correlation of the HLA profile with age of onset, severity and duration of the disease, presence of ophiasis, and family history. METHODS: A total of 88 patients with alopecia areata, alopecia totalis, or alopecia universalis were compared with 100 healthy controls. HLA typing was performed by the Terasaki microlymphocytotoxicity method. RESULTS: The frequency of HLA-A1, HLA-B62(15), HLA-DQ1, and HLA-DQ3 was significantly higher in patients than in controls. HLA-DR16 was significantly less common in patients than in the control group, and we concluded that this allele might have a protective role for alopecia areata. Juvenile onset and severe involvement were related with HLA-Cw7 and HLA-DR1, respectively. The HLA profile was independent of the existence of long-standing disease, presence of ophiasis, and a positive family history. CONCLUSIONS: In HLA-alopecia areata association, ethnic differences may play a role.     

Genetic association of HLA-DQB1 and HLA-DRB1 polymorphisms with alopecia areata in the Italian population

Background Alopecia areata (AA) is a multifactorial disease characterized by hair loss especially from the scalp. As for other autoimmune conditions, the major histocompatibility complex (HLA) region is associated with AA susceptibility. Objective To provide evidence for the association of specific HLA‐DQB1 and HLA‐DRB1 alleles with AA in an Italian population, using a case–control approach. Methods We performed a case–control study to investigate whether HLA‐DQB1 and ‐DRB1 alleles predispose to AA in the Italian population. HLA class II typing was performed in 85 patients with AA and 210 healthy controls from the same ethnic group. Results An increased frequency of DQB1*03, coding for DQ7 heterodimers, and a decreased rate of the DQB1*06 allele were observed in patients when compared with controls; the greatest and significant difference was in the group of cases with a more severe phenotype [AA > 50% patients (more than 50% hair loss) vs. controls, P = 4·5 × 10^?3, P_c = 0·031, odds ratio (OR) 2·01, 95% confidence interval (CI) 1·22–3·31 and P = 2·5 × 10^?3, P_c = 0·017, OR 0·22, 95% CI 0·07–0·72, respectively]. DQB1*03, serologically related to DQ8 or coding for DQ9 molecules, was not associated with AA susceptibility. Out of all patients, 65·9% carried DQ7 heterodimers compared with 49·5% of the controls (P = 7·3 × 10^?3, OR 1·97, 95% CI 1·17–3·32) and DQ7 prevalence rose to 76·3% in patients with AA > 50% (P = 1·7 × 10^?3, OR 3·28, 95% CI 1·48–7·27). No significant difference was found in the distribution of DRB1 variants or phenotypes among cases and controls. Conclusion Our data show a correlation between the HLA‐DQB1 locus and the occurrence of AA in Italy supporting DQB1*03(DQ7) as a predisposing allele for the disease and the relevance of the HLA genetic test in the clinical management of AA.     

Association of HLA class I alleles with aloplecia areata in Chinese Hans

BACKGROUND: Some studies suggested that human HLA status may potentiate development of the AA phenotype and exists ethic differences. No report has been published about HLA class I alleles associated with AA in Chinese Hans. OBJECTIVE: To study the distribution of HLA class I alleles and haplotypes in Chinese Hans AA patients and the relation of HLA class I profile with age of onset, severity, duration of current attack, past history and family history. METHODS: The polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA class I alleles in 192 patients with AA and 252 healthy controls in Chinese Hans. RESULTS: The frequencies of HLA-A*02, -A*03, -B*18, -B*27, -B*52 and -Cw*0704 were significantly higher in patients than in controls. The A*2-B*18, A*2-B*27, A*2-B*52, A*2-Cw*0704, B*18-Cw*0704, B*27-Cw*0704, B*52-Cw*0704 were found as high-risk haplotypes in developing AA in this study. The HLA-A*02 and -A*03 were observed increased frequencies in patients less than 50% hair loss, and HLA-B*27 equally in patients of 50-99% hair loss, alopecia totalis and alopecia universalis. The frequencies of HLA-A*02 and -B*27 were significantly raised in recurrent patients, and ones of HLA-A*02, -A*03 and -B*27 similarly in patients without a positive family history. CONCLUSION: This study demonstrated the positive association of HLA class I alleles and haplotypes with AA. There may be differences in genetic background in patients with different age of onset, grade of scalp hair loss, duration of current attack, a past history and a family history.     

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles

Background  Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes.
Objectives  The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form.
Methods  Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped.
Results  Firstly, when the whole patient population was studied, DRB1*03 , DQB1*0302 and DRB1*04 alleles were significantly associated with the disease while a significant decrease of, in particular, DRB1*11 and DQB1*0301 was observed in patients compared with controls. DRB1*0301 was the dominant allele in DR3-positive patients and controls, while DRB1*0402 was found in 42% of DR4-positive patients. Secondly, when the HLA DR/DQ allele distribution was studied after dividing patients according to their geographical origin, the southern group, which consisted exclusively of patients with the endemic form of the disease, showed the same associations as the whole pemphigus foliaceus population, particularly with DRB1*03 . In the northern group, only the DRB1*04 and DQB1*0301 alleles were found to be associated. Interestingly, anti-desmoglein 1 antibody-positive healthy controls did not carry susceptibility alleles but, in contrast, most carried negatively associated alleles.
Conclusions  These observations indicate that a particular genetic background characterizes the Tunisian endemic form of pemphigus foliaceus and that HLA class II genes control the pathogenic properties of the autoimmune response rather than the initial breakage of B-cell tolerance.     

Investigation of the HLA-DRB1 locus in alopecia areata

To further evaluate the nature of the HLA association with alopecia areata (AA), we investigated the HLA-DRB1 locus in 161 AA patients and 165 matched controls from Belgium and Germany. HLA-DRB1 typing was performed using a recently established method that employs a combination of PCR-SSP (sequence specific priming) and Pyrosequencing(TM) technology. No significant differences were observed for HLA allele groups DRB1 *01, *07, *08, *09, *10, *11, *13, *14, *15, and *16. HLA-DRB1*03 was found to confer a protective effect (7.5% versus 13.6%, p = 0.011). Additional genotyping at the allelic level revealed a significant difference in HLA-DRB1*0301 between patients and controls (6.8% versus 11.2%, p = 0.048). The DRB1*04 allele group was confirmed as a risk factor for the development of AA (20.8% versus 13.3%, p = 0.012), with the allele DRB1*0401 accounting for the greatest proportion of the effect (13.4% versus 7.3%, p = 0.014). Results obtained after subgrouping of the patients according to age at onset, severity and family history of the disease suggests that the genetic effects of the HLA system are strongest in familial cases of the disease.     

Human leucocyte antigen class II associations in chronic idiopathic urticaria

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases. Recent investigations have shown about 30% of patients with chronic idiopathic urticaria (CIU) have IgG autoantibodies against the high-affinity IgE receptor, FcepsilonRI, or IgE. A link between MHC class II alleles and CIU has not been reported previously. DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined using the polymerase chain reaction with sequence-specific primers, testing for DRB and DQB1 alleles. The frequency of alleles in CIU patients was compared with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intradermal injection of autologous serum and their serum-induced histamine release from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 (DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10-5 and P = 2 x 10-4, respectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), are significantly less frequently associated with CIU. The HLA DRB1*04 association is particularly strong (corrected P = 3.6 x 10-6) for patients whose serum has in vivo and in vitro histamine-releasing activity. HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.     

Human leukocyte antigen region involvement in the genetic predisposition to alopecia areata

Human leukocyte antigens (HLA) of classes I and II were studied in 127 patients with alopecia areata (AA). The patients were subdivided into different groups depending on hair loss area, sex, pathogenesis, response to topical immune modulators (squaric acid dibutylester and diphencyprone) and age of onset of the disease. The frequencies of class I HLA markers (loci A, B, C) were not significantly different from the controls. However, among the class II antigens (loci DR, DQ), the frequency of DR5 was increased in both alopecia areata and alopecia universalis when compared with the control group. In particular, DR5 was strongly linked to the early-onset form. The highest DR5 frequency (62%) was found in the group of patients which presented both the early onset and the most severe form of the disease (p less than 0.01; RR = 3.14). A decrease of the HLA-B8 phenotype frequency was found in the alopecia areata group versus the alopecia universalis one. No significant deviation was found between the female patients and the control group. However, an increase of CW3 and a decrease of DR1 was seen in the males. In the group including 'combined', 'prehypertensive', 'atopic' alopecia of Ikeda's classification the frequency of HLA-A28 and DR5 was increased and that of DR1 was decreased in comparison with the 'common' type of alopecia and the controls. It was not possible to find any relationship between these genetic markers and the response to topical immune modulators.     

PUVA treatment of alopecia areata

Twenty-three patients with alopecia areata were treated with photochemotherapy combining oral or topical methoxsalen and UV-A irradiation of the scalp or of the whole body. Eleven of 17 patients with multiple plaques of alopecia areata, alopecia totalis, and alopecia universalis, who were treated with oral methoxsalen and total body irradiation, had complete or more than 90% hair regrowth. Three patients had a relapse. The mean energy required was 505 joules/sq cm. In six cases, topical applications of methoxsalen or oral methoxsalen combined with local irradiation of the scalp were treatment failures. In the patients responding to treatment, the result did not seem to depend on the age of onset or the extent or duration of disease. However, patients with long-lasting alopecia had a higher risk of recurrence notwithstanding a good initial regrowth of hair. Few side effects of psoralens and UV-A (PUVA) treatment were noted. The mean follow-up period was 18.6 months after the completion of treatment. We discuss the possible mechanisms of action of PUVA in the treatment of alopecia areata.     

Correlation between HLA and pityriasis rosea susceptibility in Brazilian blacks

Objectives The human leucocyte antigen (HLA) has been related to susceptibility factors in several diseases. This study aimed to determine the potential genetic susceptibility of patients with pityriasis rosea (PR) through HLA molecular typing analysis. Methods The method of choice was polymerase chain reaction with sequence‐specific primers (PCR‐SSP) using low‐resolution typing kits, with determination of the alleles class I (HLA‐A, HLA‐B and HLA‐C) and class II (HLA‐DRB1, DRB3, DRB4, DRB5 and DQB1) performed in 30 Afro‐Brazilian PR‐diagnosed patients and 45 healthy individuals as the control group (PR‐C). Results Analysis of the HLA typing results showed that the relative risk (RR) of 4.00 [95% confidence interval (95% CI) 1.20–13.28, two‐tailed P = 0.018] for allele HLA‐DQB1*04 class II, detected in 33.3% of PR patients, was significant. By contrast, in the control group only 11.1% of subjects had that allele. Three out of six B*51 alleles and three out of six B*53 alleles detected in PR patients were found, together with the allele DQB1*04. Conclusion We suggest that alleles DQB1*04 may be involved in the genetic susceptibility of PR based on the significant predominance of those alleles observed in the black PR patients. We also recommend that more studies are conducted on populations of other ethnic origins, preferentially with higher resolution techniques of DNA typing.     

华东地区汉族斑秃与HLA-DRB1*03、*04、*11基因多态性的关联研究

目的 探讨中国华东地区汉族人群HLA-DRB1基因与斑秃发病、临床特点的关系。方法 采用序列特异性引物PCR（PCR-SSP）技术对已确诊为斑秃的158例和正常人对照组172例进行HLA-DRB1基因多态性分析。并比较斑秃患者不同发病年龄、发病次数、病程、家族史及严重程度与HLA-DRB1基因的关联性。结果 斑秃组HLA-DRB1*03、HLA-DRB1*11等位基因频率与对照组差异无统计学意义。斑秃组HLA-DRB1*04（OR = 1.99,Pc = 0.01）等位基因频率明显高于对照组。与正常人对照组比较,斑秃晚发组（发病年龄 > 16岁）（OR = 1.94,Pc = 0.02）、斑秃复发组（发病次数 > 1）和初发组（OR = 2.49、Pc = 0.02,OR = 1.83、Pc = 0.04）、病程 > 1年的患者（OR = 2.94,Pc = 0.01）、无家族史的患者（OR = 1.97,Pc = 0.02）、严重斑秃患者（OR = 3.53,Pc = 0.00）HLA-DRB1*04等位基因频率均显著升高。结论 中国华东地区汉族人群HLA-DRB1*04等位基因与斑秃发病、临床分型显著相关。     

Alopecia Areata

Alopecia areata is a common form of non-scarring alopecia that appears equally in males and females of any age, although children and adolescents are more commonly affected. The disorder is usually characterized by limited alopecic patches on the scalp, but more severe forms may affect the entire scalp (alopecia totalis) or body (alopecia universalis). Characteristic nail changes may also accompany hair loss. Alopecia areata has been linked with certain human leukocyte antigen (HLA) class II alleles, indicating a probable autoimmune etiology. Current research implicates T lymphocytes in the pathogenetic mechanism of disease. Other autoimmune diseases are also linked with alopecia areata. The diagnosis of alopecia areata is usually made clinically, although a biopsy is diagnostic for this condition. Treatment is challenging and aims at the regrowth of hair in affected individuals. Intralesional corticosteroid injections are widely used in mild disease. Topical anthralin and minoxidil may also be clinically efficacious. Topical sensitizers, such as squaric acid dibutlyester and diphenylcyclopropenone, are sometimes employed. Various therapies for the disease may have efficacy in different patients, making a universal treatment algorithm difficult to implement. Patients should be handled on an individual basis, with the final outcome based on the cosmetic regrowth of hair. Maintenance therapy is also important in patients that do achieve acceptable regrowth, necessitating a highly motivated patient and good rapport with the treating physician.     

Antibodies against hair follicles are associated with alopecia totalis in autoimmune polyendocrine syndrome type I

In the autosomal recessively inherited autoimmune polyendocrine syndrome type I (APS I) patients have autoantibodies directed against several endocrine and nonendocrine organs. Alopecia areata is present in about one-third of the patients and usually in the more severe forms, alopecia universalis or totalis. Sera from 39 patients with APS I, diluted 1:150, were used in indirect immunofluorescence staining of cryo-sections from normal human scalp. Two hair follicle staining patterns were observed. A cytoplasmic staining of the differentiating matrix, cuticle, and cortex keratinocytes in the anagen hair follicle was seen in five (13%) APS I sera. All these five patients had alopecia totalis, representing 63% of the eight patients with alopecia totalis (p < 0.0001). Furthermore, four (10%) of the APS I sera stained the nuclei of the melanocytes in the hair follicle. Two of these patients had vitiligo. None of 20 healthy control sera stained the keratinocyte cells or the melanocyte nuclei. These data show that many patients with APS I have high-titer autoantibodies directed against the anagen matrix, cuticle, and cortex keratinocytes and a melanocyte nuclear antigen, and also that the hair follicle keratinocyte staining is associated with alopecia, especially alopecia totalis. This study emphasizes the role of the differentiating anagen keratinocytes as an important structure in the autoimmune etiology of alopecia, both in APS I and at least in a subgroup of patients with alopecia areata unrelated to APS I.     

Five‐year experience in the treatment of alopecia areata with DPC

Background The effectiveness of Diphencyprone (DPC) in alopecia areata (AA) was demonstrated in several studies with highly variable response rates ranging from 5% to 85%. Objective The response rate and variable factors affecting the prognosis were studied focusing on long‐term follow‐up with or without maintenance therapy. Methods A total of 135 cases of AA were treated with DPC. Patients were divided into five groups according to the area of scalp affected: Grade 1 AA: 25–49% scalp affection; Grade 2 AA: 50–74% scalp affection; Grade 3 AA: 75–99% scalp affection; alopecia totalis and alopecia universalis. An initial response was defined as appearance of new terminal hair within treated sites. Excellent response was defined as terminal hair covering >75% of the scalp. Relapse meant >25% hair loss. Maintenance therapy meant ongoing therapy once every 1–4 weeks after excellent response. Follow‐up was performed to detect any relapse of AA. Results Ninety‐seven patients continued therapy for ≥3 months. After an initial 3 month lag, cumulative excellent response was seen in 15 patients (15.4%), 47 patients (48.5%), 51 patients (52.6%) and 55 patients (55.7%) after 6, 12, 18 and 24 months respectively in a mean median time of 12 months. The only patient variable affecting the prognosis was baseline extent of AA. Excellent response was seen in 100%, 77%, 54%, 50% and 41% in Grade 1, Grade 2, Grade 3, AA totalis and AA universalis patients respectively. Side‐effects were few and tolerable. Hair fall >25% occurred in 17.9% of patients on maintenance and 57.1% of patients without maintenance therapy (P‐value = 0.025). Conclusion Diphencyprone is an effective and safe treatment of extensive AA. A long period of therapy is needed and will increase the percentage of responders especially in alopecia totalis and universalis. Maintenance therapy is recommended to reduce the risk of relapse.     

Direct immunofluorescence studies in alopecia areata and male pattern alopecia.

Direct immunofluroescence studies were performed on hairy and alopecic areas of scalp in patients with alopecia areata, alopecia totalis and male pattern alopecia. Abnormal deposits of C3 and occasionally of IgG and IgM were found in 92% of 12 patients with alopecia areata and in 21% of patients with male pattern alopecia. No abnormalities were seen in 4 patients with alopecia totalis. In both alopecia areata and male pattern alopecia, the deposits were most common along the basement zone of the inferior segment of hair follicles and occurred with equal frequency in alopecic and normal scalp. These observations suggest that immune factors may play a role in the pathogenesis of alopecia areata.