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UPDATES IN PSYCHOSOMATIC MEDICINE AND CONSULTATION-LIAISON PSYCHIATRY
Primary Psychiatry. 2008;15(12):28-30

Psychiatric Issues in Dermatology, Part 3: Acne Vulgaris and Chronic Idiopathic Pruritus
James L. Levenson, MD

T

his column continues a series reviewing the interface between dermatology and psychiatry. Dermatologists and primary care physicians frequently encounter important psychiatric issues affecting diagnosis and management of patients with dermatologic complaints. Psychological factors affect many dermatologic conditions, including atopic dermatitis, psoriasis, alopecia areata, urticaria and angioedema, and acne vulgaris. Some dermatologic conditions are best considered as 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, delusions 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, or that 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. More detailed coverage of these topics can be found elsewhere.1,2 The first part of the series focused on atopic dermatitis and psoriasis,3 and the second reviewed alopecia areata, urticaria, and angioedema.4 This third installment reviews acne vulgaris and chronic idiopathic pruritus.

ACNE VULGARIS
Acne vulgaris, a common skin disease affecting sebaceous glands with sebum blocking hair follicles, is characterized by a variety of lesions, including comedones, inflammatory papules, pustules, and nodules. The face and upper neck are the most common sites, but the chest, back, and shoulders may also be involved. Most cases of acne vulgaris develop in early adolescence, affecting 85% of teenagers, and it frequently continues into adulthood. During adolescence, the frequency of acne increases with age and pubertal development. In girls, the commencement of menstruation is associated with increased frequency of acne. Perhaps this explains why adolescent girls may be more vulnerable than boys to the negative psychological effects of acne.5 The course of acne vulgaris is usually self-limited, with gradual improvement and spontaneous disappearance after several years, but it may persist into the thirties and

forties. Possible complications include development of pitted or hypertrophic scars as well as psychological adverse effects, discussed below. Although women are more likely than men to have persistent acne, it tends to be more severe in men.1,2 Although the cause of acne vulgaris is unknown, many factors are probably involved in its pathogenesis, including genetics, inflammation, skin flora, hormonal activity, and stress. The relationship with stress has long been observed, but there are few prospective studies. One study6 reported that patients with acne may experience worsening of the disease during academic examinations. While there is a significant association between psychological stress and severity of acne, it does not appear to be mediated by increased sebum production.7 A variety of neuroendocrine mediators may be involved in the precipitation or aggravation of acne by stress, including adrenal steroids, corticotropin-releasing hormone, melanocortins, β-endorphin, vasoactive intestinal polypeptide, neuropeptide Y, insulin-like

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.

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growth factor, and calcitonin gene-related peptide.1,2,8 It has also been long recognized that lithium can cause or aggravate acne,9 and there have been case reports of acne resulting from aripiprazole,10 lamotrogine,11 valproate,12 and other anticonvulsants, as well as the atypical tricyclic antidepressant amineptine13 (not available in the United States). Severe acne is associated with increased depression, anxiety, poor self-image, and poor self-esteem.1,2 Not surprisingly, psychiatric symptoms are more common in more severe acne and in the later stages of puberty.14 A cross-sectional study15 of approximately 10,000 teenagers in New Zealand found that “problem acne” was associated with an increased risk of depressive symptoms (odds ratio 2.04), anxiety (odds ratio 2.3), and suicide attempts (odds ratio 1.83). The association of acne with suicide attempts remained after controlling for depressive symptoms and anxiety (odds ratio 1.5). One study16 has estimated the incidence of suicidal ideation in patients with acne as 7.1%. However, psychiatric comorbidity may even occur with milder acne. A Turkish study17 found that patients with acne were at increased risk for anxiety and depression compared to the normal population, irrespective of the degree of severity. Acne can substantially interfere with social and occupational functioning and result in impairment in quality of life (QOL). There are numerous available rating scales for quantifying QOL in patients with acne.18 Acne negatively affects quality of life, and there is not always a correlation between the severity of acne and its impact on QOL. The magnitude of anxiety and depression is proportional to degree of impairment of QOL due to acne.17 Acne patients with greater social sensitivity experience poorer QOL compared to other patients with the same severity of acne.19 Anger, similarly, is associated with poorer QOL and less satisfaction with treatment, independent of other variables.20 Successful treatment of acne with isotretinoin leads to reduction in anxiety and depression and significant improvement in self-image.1,2 However, patients’ perceptions of the results of treatment for acne can differ from their physician’s judgment, with more pessimistic self-assessment in those with emotional distress.21 Anecdotal reports of depression, suicidal ideation, suicide attempts, and suicide with the use of isotretinoin for treatment of acne vulgaris were widely reported in the media and led the US Food and Drug Administration to expand the label warning to include that “accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors.”22 However, a recent systematic review23 of nine controlled trials found that rates of depression among isotretinoin users were similar to the rates
Primary Psychiatry © MBL Communications

in oral antibiotic control groups, ranging from 1% to 11%. Trials that compared depression before and after isotretinoin treatment did not show a statistically significant increase in depression symptoms or diagnoses. Some even found a trend toward reduction in depressive symptoms after isotretinoin therapy, particularly in patients with higher pretreatment depression scores. Similar reductions have been reported in uncontrolled trials.24 Another recent study25 in Canada using a retrospective case-crossover design found that, the relative risk for those exposed to isotretinoin of developing a depression diagnosis was 2.68 (95% CI=1.10–6.48), after adjusting for confounders. In contrast, another Canadian group26 recently reported a prospective controlled cohort study that concluded that isotretinoin does not appear to be associated with the development of depression. The literature to date has not proven a causative association between isotretinoin use and depression or suicidal behavior. Interpretation of the literature is complicated both by important methodologic limitations in many of the studies and by the association of acne itself with depression, anxiety, and possibly suicidal behavior. The FDA and isotretinoin’s manufacturer subsequently added a warning regarding the possible development of aggressive and/or violent behavior to the psychiatric disorder warning section of the package insert previously focused on depression and suicidality. While there have been reports of several cases of manic psychosis in association with isotretinoin treatment,27 large population-based cohort studies have found no evidence that use of isotretinoin is associated with an increased risk for psychosis.28 One may ask how clinicians should proceed, given the FDA’s black box warning and the case reports suggesting an association between isotretinoin and depression and suicide, yet an overall lack of support for these associations in the more rigorous observational and epidemiologic studies. It is prudent to continue to prescribe isotretinoin to treat severe acne, while at the same time educating patients (and the parents of minor patients) of the importance of actively monitoring for depressive symptoms; if symptoms appear, referral to a psychiatrist and discontinuation of isotretinoin should be considered. In addition, patients should be cautioned not to self-medicate for depression with St. John’s Wort both because it is ineffective and because its metabolic interaction with hormonal contraceptives may reduce their effectiveness. Numerous reports attest to the benefits of a wide variety of psychiatric and psychological treatments for acne, including paroxetine,29 olanzapine,30 relaxation techniques, hypnosis, cognitive-behavioral therapy, and biofeedback,31,32 but no controlled clinical trials except for one.33

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CHRONIC IDIOPATHIC PRURITUS
Pruritus, or itchiness, is a common symptom of dermatologic diseases, several systemic diseases (eg, hepatic or renal failure, HIV), and advanced age,1,2 but the cause in chronic pruritus is often not identifiable. Such idiopathic pruritus is typically experienced on a daily basis, especially at night and in the evening, resulting in mostly having difficulty falling asleep. Generalized idiopathic pruritus mainly involves the legs, arms, and back. The most common focal presentations of idiopathic pruritus are pruritus ani, vulvae, and scroti. Idiopathic pruritus may be described as crawling, tickling, stinging, or burning.34,35 In one study,34 idiopathic pruritus patients described the itching as unbearable (73%), bothersome (72%), annoying (67%) and/or worrisome (45%). The pathophysiology of pruritus is not well understood, and it is unclear why it is worse at night.36 While psychiatric symptoms are common in idiopathic pruritus, and idiopathic pruritus is common in psychiatric patients, idiopathic pruritus should be considered as a functional disorder rather than a psychogenic one. New onset of unexplained pruritus should lead to evaluation for occult medical disease before considering it to be idiopathic pruritus. Recent stressful life events, and degree of anxiety and/or depressive symptoms have been correlated with an increased ability to experience itching.1,2 In a study37 of 100 psychiatric inpatients, idiopathic pruritus was reported by 42% of the subjects, 34% of the men, and 58% of the women, with increased prevalence in those without adequate social support and in those without regular employment. It is not surprising that depression is common in patients with idiopathic pruritus, especially given the chronicity and sleep disturbance.38 For focal idiopathic pruritus (eg, pruritus ani, vulvae, and scroti), topical treatments are used. For both generalized and focal idiopathic pruritus, the most commonly prescribed oral medications are antihistamines, which usually provide some short-term relief. Tricyclic antidepressants, especially doxepin, can relieve chronic idiopathic pruritus. Paroxetine has also been reported to be helpful.39 Opiate receptor antagonists and anticonvulsants (gabapentin, pregabalin, carbamazepine) have also been suggested as possible remedies.40 Behavioral treatment, such as habit-reversal training and cognitive-behavioral therapy, may also be helpful in interrupting the itch-scratch cycle,1,2 and there is one case report of the benefits of hypnosis.41 PP

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3. Levenson JL. Psychiatric issues in dermatology, part 1: atopic dermatitis and psoriasis. Primary Psychiatry. 2008;15(7):35-38. 4. Levenson JL. Psychiatric issues in dermatology, part 2: alopecia areata, urticaria and angioedema. Primary Psychiatry. 2008;15(9):31-34. 5. Aktan S, Ozmen E, Sanli B. Anxiety, depression, and nature of acne vulgaris in adolescents. Int J Dermatol. 2000;39(5):354-357. 6. Chiu A, Chon SY, Kimball AB. The response of skin disease to stress: changes in the severity of acne vulgaris as affected by examination stress. Arch Dermatol. 2003;139(7):897-900. 7. Yosipovitch G, Tang M, Dawn AG, et al. Study of psychological stress, sebum production and acne vulgaris in adolescents. Acta Derm Venereol. 2007;87(2):135-139. 8. Zouboulis CC, Böhm M. Neuroendocrine regulation of sebocytes—a pathogenetic link between stress and acne. Exp Dermatol. 2004;13(suppl 4):31-35. 9. Yeung CK, Chan HH. Cutaneous adverse effects of lithium: epidemiology and management. Am J Clin Dermatol. 2004;5(1):3-8. 10. Mishra B, Praharaj SK, Prakash R, Sinha VK. Aripiprazole-induced acneiform eruption. Gen Hosp Psychiatry. 2008;30(5):479-481 11. Nielsen JN, Licht RW, Fogh K. Two cases of acneiform eruption associated with lamotrigine. J Clin Psychiatry. 2004;65(12):1720-1722. 12. de Vries L, Karasik A, Landau Z, Phillip M, Kiviti S, Goldberg-Stern H. Endocrine effects of valproate in adolescent girls with epilepsy. Epilepsia. 2007;48(3):470-477. 13. De Gálvez Aranda MV, Sánchez PS, Alonso Corral MJ, Bosch García RJ, Gallardo MA, Herrera Ceballos E. Acneiform eruption caused by amineptine. A case report and review of the literature. J Eur Acad Dermatol Venereol. 2001;15(4):337-339. 14. Kilkenny M, Stathakis V, Hibbert ME, Patton G, Caust J, Bowes G. Acne in Victorian adolescents: associations with age, gender, puberty and psychiatric symptoms. J Paediatr Child Health. 1997;33(5):430-433. 15. Purvis D, Robinson E, Merry S, Watson P. Acne, anxiety, depression and suicide in teenagers: a cross-sectional survey of New Zealand secondary school students. J Paediatr Child Health. 2006;42(12):793-796. 16. Picardi A, Mazzotti E, Pasquini P. Prevalence and correlates of suicidal ideation among patients with skin disease. J Am Acad Dermatol. 2006;54(3):420-426. 17. Yazici K, Baz K, Yazici AE, et al. Disease-specific quality of life is associated with anxiety and depression in patients with acne. J Eur Acad Dermatol Venereol. 2004;18(4):435-439. 18. Dréno B. Assessing quality of life in patients with acne vulgaris: implications for treatment. Am J Clin Dermatol. 2006;7(2):99-106. 19. Krejci-Manwaring J, Kerchner K, Feldman SR, Rapp DA, Rapp SR. Social sensitivity and acne: the role of personality in negative social consequences and quality of life. Int J Psychiatry Med. 2006;36(1):121-130. 20. Rapp DA, Brenes GA, Feldman SR, et al. Anger and acne: implications for quality of life, patient satisfaction and clinical care. Br J Dermatol. 2004;151(1):183-189. 21. Jones-Caballero M, Pedrosa E, Peñas PF. Self-reported adherence to treatment and quality of life in mild to moderate acne. Dermatology. 2008;217(4):309-314. 22. FDA Approved Drug Products. Available at: www.accessdata.fda.gov/scripts/cder/drugsatfda/index. cfm?fuseaction=Search.Label_ApprovalHistory. Accessed September 24, 2008. 23. Marqueling AL, Zane LT. Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Semin Cutan Med Surg. 2007;26(4):210-220. 24. Kaymak Y, Kalay M, Ilter N, Taner E. Incidence of depression related to isotretinoin treatment in 100 acne vulgaris patients. Psychol Rep. 2006;99(3):897-906. 25. Azoulay L, Blais L, Koren G, LeLorier J, Bérard A. Isotretinoin and the risk of depression in patients with acne vulgaris: a case-crossover study. J Clin Psychiatry. 2008;69(4):526-532. 26. Cohen J, Adams S, Patten S. No association found between patients receiving isotretinoin for acne and the development of depression in a Canadian prospective cohort. Can J Clin Pharmacol. 2007;14(2):e227-e233. 27. Barak Y, Wohl Y, Greenberg Y, et al. Affective psychosis following Accutane (isotretinoin) treatment. Int Clin Psychopharmacol. 2005;20(1):39-41. Erratum in: Int Clin Psychopharmacol. 2005;20(3):182. 28. Jick SS, Kremers HM, Vasilakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol. 2000;136(10):1231-1236. 29. Moussavian H. Improvement of acne in depressed patients treated with paroxetine. J Am Acad Child Adolesc Psychiatry. 2001;40(5):505-506. 30. Gupta MA, Gupta AK. Olanzapine may be an effective adjunctive therapy in the management of acne excoriée: a case report. J Cutan Med Surg. 2001;5(1):25-27. 31. Shenefelt PD. Using hypnosis to facilitate resolution of psychogenic excoriations in acne excoriée. Am J Clin Hypn. 2004;46(3):239-245. 32. Shenefelt PD. Biofeedback, cognitive-behavioral methods, and hypnosis in dermatology: is it all in your mind? Dermatol Ther. 2003;16(2):114-122. 33. Hughes H, Brown BW, Lawlis GF, Fulton JE Jr. Treatment of acne vulgaris by biofeedback relaxation and cognitive imagery. J Psychosom Res. 1983;27(3):185-191. 34. T-J Goon A, Yosipovitch G, Chan YH, Goh CL. Clinical characteristics of generalized idiopathic pruritus in patients from a tertiary referral center in Singapore. Int J Dermatol. 2007;46(10):1023-1026. 35. Yosipovitch G, Ansari N, Goon A, Chan YH, Goh CL. Clinical characteristics of pruritus in chronic idiopathic urticaria. Br J Dermatol. 2002;147(1):32-36. 36. Patel T, Ishiuji Y, Yosipovitch G. Nocturnal itch: why do we itch at night? Acta Derm Venereol. 2007;87(4):295-298. 37. Kretzmer GE, Gelkopf M, Kretzmer G, Melamed Y. Idiopathic pruritus in psychiatric inpatients: an explorative study. Gen Hosp Psychiatry. 2008;30(4):344-348. 38. Sheehan-Dare RA, Henderson MJ, Cotterill JA. Anxiety and depression in patients with chronic urticaria and generalized pruritus. Br J Dermatol. 1990;123(6):769-774. 39. Zylicz Z, Krajnik M, Sorge AA, Costantini M. Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial. J Pain Symptom Manage. 2003;26(6):1105-1112. 40. Lynde CB, Kraft JN, Lynde CW. Novel agents for intractable itch. Skin Therapy Lett. 2008;13(1):6-9. 41. Rucklidge JJ, Saunders D. Hypnosis in a case of long-standing idiopathic itch. Psychosom Med. 1999;61(3):355-358.

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