Dr. Levenson is professor in the Departments of Psychiatry, Medicine, and Surgery, chair of the Division of Consultation-Liaison Psychiatry, and vice chair for clinical affairs in the Department of Psychiatry at Virginia Commonwealth University School of Medicine in Richmond.
Disclosure: Dr. Levenson reports no affiliation with or financial interest in any organization that may pose a conflict of interest.
This column continues a series reviewing the interface between dermatology and psychiatry. Part one focused on atopic dermatitis and psoriasis.1 This second installment reviews alopecia areata, urticaria, and angioedema. Dermatologists and primary care physicians frequently encounter important psychiatric issues affecting diagnosis and management of the patient with dermatologic complaints. Psychiatrists contend with frequent pruritus and rashes in their patients. A study of psychiatric inpatients that excluded those with known skin diseases found that 33% of patients reported itching.2 Psychological factors affect many dermatologic conditions including atopic dermatitis, psoriasis, alopecia areata, urticaria and angioedema, and acne vulgaris. Some dermatologic conditions are best considered idiopathic functional disorders, such as idiopathic pruritus, which can be generalized or focal (eg, pruritus ani, vulvae, and scroti). Some primary psychiatric disorders present with primarily physical symptoms to dermatologists, including body dysmorphic disorder (BDD) and delusional disorder, somatic type (eg, delusions of parasitosis or of a foul body odor). Indeed, most patients with delusions of parasitosis or BDD avoid seeing psychiatrists or other mental health professionals and resist referral. Dermatologists also see patients with compulsive behaviors that may be part of obsessive-compulsive disorder (OCD), or stand alone (eg, trichotillomania, psychogenic excoriation, and onychophagia). Factitious skin disorders include factitious dermatitis (also called dermatitis artefacta) and psychogenic purpura. Another important aspect of the interface between psychiatry and dermatology is the range of dermatologic adverse reactions to psychotropic drugs.3,4
Alopecia areata is characterized by nonscarring hair loss in patches of typically well-demarcated smooth skin, most noticeably on the scalp but the eyebrows, eyelashes, beard, and body hair can all be affected. Involvement varies from a single patch to multiple patches or total hair loss. It can affect the entire scalp (alopecia totalis) or cause loss of all body hair (alopecia universalis). Breakage of the hair shaft results in characteristic “exclamation-mark” hairs. The peak incidence of alopecia areata is in the third to fifth decades of life. It is a relatively common condition affecting 0.15% of the population. Approximately 1% of the United States population will have at least one episode by 50 years of age, with equal incidence in men and women. One-third of patients with alopecia areata completely recover after a single episode, but the rest have recurrences or never recover from the first episode. Although in many cases it can be a self-limiting condition, hair loss can often have severe social and emotional impacts.
Alopecia Areata and Stress
Alopecia areata was at one time considered a “psychosomatic illness” because of the apparent influence of stress on the disorder and the frequency of comorbid psychiatric symptoms. However, empirical literature has shown mixed results and debate continues about the role of psychiatric factors in the development of alopecia areata.3,4 Some recent studies described here will convey the complexity of the issues.
A case-control study comparing adults with alopecia areata to controls with skin diseases considered unaffected by stress reported that 66% of those with alopecia areata had experienced stressful events compared to 22% of controls (odds ratio=7.75). Alopecia areata patients also had a higher mean number of stressful life events. Especially common in patients with alopecia areata were family problems (45.6% of subjects) and personal problems (35.7% of subjects).5
Another cross-sectional case-control study6 of 52 adult patients diagnosed with alopecia areata and 52 age- and sex-matched individuals without any hair loss found no statistically significant difference between the patient and control groups with regard to the total scores of stressful major life events, depression, or anxiety. The total number of stressful life events was higher in patients who attributed their disease to a stressful life event than in those who did not, but this could either indicate that stressful life events may act as a trigger in a subset of patients, or a reporting bias. A similar case-control study7 found an increase in stressful life events in patients with recurrent alopecia areata but not in those with first episodes. A significantly higher degree of trait-anxiety and perceived distress were observed among patients in both alopecia groups compared to the control subjects, but these results do not allow any conclusions about causality.
Psychosocial Morbidity in Alopecia Areata
A small cross-sectional study8 found that 66% of patients with alopecia areata had psychiatric comorbidity, mainly adjustment disorders, generalized anxiety disorder, and depressive episodes. The patients’ overall adaptation to the illness was satisfactory, showing few adverse effects in family or social life, work, or sexual adjustment. Poor adjustment was associated with a dependent or antisocial personality, generalized anxiety, and depression.8
There has been little attention in the literature to the psychosocial consequences of alopecia areata in children. A small case-control cross-sectional study9 in children with alopecia areata compared with control children who visited a pediatrician “for a mild condition,” reported that the children with alopecia were more anxious, depressed, withdrawn, aggressive, and/or delinquent. They had more inattention, somatic complaints, and problems in social relations. Girls with alopecia appeared to more adversely psychologically affected than boys.
Alopecia Areata Treatments
A 2008 Cochrane review10 of treatment for alopecia areata concluded that very few treatments for alopecia areata have been well evaluated in randomized trials. No randomized controlled trials could be found establishing efficacy of the most commonly used oral or topical dermaceuticals. Most of the published trials are so small, brief, and flawed that any important clinical benefits are inconclusive. Delamere and colleagues10 concluded, “Considering the possibility of spontaneous remission especially for those in the early stages of the disease, the options of not being treated therapeutically or, depending on individual preference wearing a wig may be alternative ways of dealing with this condition.”
Psychiatric and Psychological Treatments for Alopecia Areata
Antidepressants have been reported in case reports to both cause and benefit alopecia areata.11-13 In a very small double-blind, placebo-controlled trial,14 patients taking imipramine 75 mg/day had significantly more hair regrowth than did control subjects, an effect that was independent of reductions in anxiety or depression. There have also been case reports of alopecia areata associated with antipsychotics.15,16 Uncontrolled studies of psychotherapy and relaxation techniques have been promising in the treatment of alopecia areata, but more study is needed. A typical example is an open trial of hypnotherapy, added as a complementary treatment or used as the only treatment for alopecia areata. Hypnosis was reported to result in improvement in anxiety and depression. In addition, scalp hair growth of 75% to 100% was seen in 12 of 28 patients, 5 of whom relapsed.17
Urticaria and Angioedema
Urticaria (hives) is characterized by circumscribed, elevated, red, usually pruritic edematous patches (wheals) involving the superficial dermis. Angioedema occurs when the edema extends into deeper tissue layers. Urticaria and angioedema are a result of the release of histamine and other vasoactive substances from mast cells or basophils. Urticaria is common, with a peak incidence between 20–40 years of age, higher in women than men.3,4 Acute urticaria is usually caused by an allergic reaction or infection, resolving spontaneously or easily treated. Some chronic or recurrent urticarias are hereditary, and some are physically induced, such as cold, solar exposure or delayed pressure urticaria. The cause of chronic urticaria or angioedema cannot be identified in the majority of cases, though autoimmune pathogenesis is suspected. Approximately 33% of patients with chronic idiopathic urticaria have circulating functional autoantibodies, but their role in the disease is unclear. Chronic idiopathic urticaria often responds poorly to standard dermatological treatment. Chronic idiopathic urticaria resolves spontaneously in 30% to 55% of patients within 5 years,18 but some patients have persistent symptoms for many years.
Urticaria and Stress
It is widely believed that stress can precipitate acute urticaria, and contribute to the pathogenesis of chronic urticarias. In one study,19 81% of patients with chronic idiopathic urticaria believed that their illnesses were due to stress. Stress so often seemed a precipitant to angioedema that for many years clinicians referred to it as angioneurotic edema. However, the evidence base for this belief about stress inducing urticaria is rather limited. Small controlled retrospective studies found that patients with chronic urticaria were more likely to have been exposed to stressful life situations before disease onset than those with fungal skin infections20 or other skin diseases.21 A larger cross-sectional study compared patients with chronic idiopathic urticaria to those with tinea pedis. In the 6 months preceding disease onset, patients with chronic idiopathic urticaria had significantly more life events, higher impact from life events, more somatic symptoms, more severe insomnia, less family support, and more negative coping tendencies. Good ego function, better coping strategies, and family support were associated with decreased frequency of urticaria.22
There are more data regarding psychiatric comorbitity in patients with chronic idiopathic urticaria (CIU), documenting higher rates of symptoms of anxiety and depression than healthy controls.23-25 A Turkish study using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition found that 49% of CIU patients had at least one Axis I diagnosis, and 45% had at least one personality disorder. The most common Axis I disorder was OCD (26%), and the most common Axis II disorder was obsessive-compulsive personality disorder (30%). OCD, major depressive disorder, and obsessive-compulsive and avoidant personality disorders were all more prevalent compared to a healthy control group.26
A similar study in Turkey22 found that 60% had psychiatric disorders, 66% of which were depressive disorders.19 The relationship between chronic idiopathic urticaria and anxiety/depression is likely bidirectional. One possible intervening factor is that both cause insomnia.22
Health-related quality of life is markedly reduced in CIU patients,19,23,27,28 to an extent comparable to that of patients with chronic heart disease.28 Quality of life is significantly more impaired in chronic urticaria patients with psychiatric comorbidity, but is not significantly affected by age, sex, the absence or presence of angioedema, or the course or cause of the urticaria.27
Treatment of Chronic Urticaria
The first step in treatment is the avoidance of identifiable underlying causative or exacerbating factors. Histamine (H) receptor antagonists remain the mainstay of oral treatment for all forms of urticaria.18 Second-generation less sedating antihistamines (loratadine, fexofenadine, and cetirizine) are first-line agents.29 Sedating antihistamines like diphenhydramine are useful for the control of chronic idiopathic urticaria if itching is causing sleep disturbance. The tricyclic antidepressant doxepin is a potent H1 and H2 antihistamine, and is considered a standard treatment option for chronic urticaria.18,30 It has been found effective at low dosage for chronic urticaria in two small randomized controlled trials, one comparing it to placebo31 and one comparing it to diphenhydramine.32 In the latter trial,32 doxepin 10 mg TID was more effective than diphenhydramine 25 mg TID. It would be especially suitable for patients with comorbid depression. It remains controversial whether the addition of an H2 receptor antagonist or a leukotriene antagonist is helpful.18 For CIU, second-line agents include cyclosporine (effective in approximately 75% of patients), oral corticosteroids, intravenous immunoglobulins, and plasmapheresis.18,30
There has been only one controlled study33 of psychological treatment of chronic idiopathic urticaria, in which hypnosis combined with relaxation techniques reduced pruritus but not the number of wheals. PP
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