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Treatment of psychodermatoses with serotonin-norepinephrine reuptake inhibitors1
POSTER DISCUSSION SESSION 495—CLINICAL DERMATOLOGY Clinical Dermatology & Other Cutaneous Disorders P33 TREATMENT OF PSYCHODERMATOSES WITH SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS Sharam S Yashar, MD, Henry Ford Medical Center, Detroit, MI, United States, Ali Moiin, MD, Comprehensive Dermatology Center, Troy, MI, United States Psychocutaneous disorders are a group challenging skin conditions, which often have an underlying psychiatric component. Dermatoses with a primary psychological or psychiatric basis include dermatitis artefacta, neurotic excoriations, prurigo nodularis, lichen simplex chronicus, acne excoriee, trichotillomania, psychogenic pruritus, and delusions of parasitosis. The most frequently associated psychiatric symptoms are depression, anxiety, and obsessive-compulsive behavior. Psychocutaneous disorders have previously been treated with antidepressants with some success. We report a case series of 15 patients with various psychocutaneous disorders in which venlafaxine, a serotonin and norepinephrine reuptake inhibitor showed a beneficial effect. By the time of initial consultation, all patients had been previously treated with numerous other oral and topical medications. Most patients had been biopsied on several occasions to exclude a primary dermatosis or an infectious etiology. The nature of the diagnosis was discussed with each patient prior to referral for a psychiatric evaluation. All patients were treated with either venlafaxine 37.5 mg twice daily or 75 mg XR once daily, while continuing with antihistamines and/or topical corticosteroids. Patients were examined at 1, 4, 8, 12, and 24-week intervals to evaluate adverse effects, psychiatric symptoms and mood, skin symptomatology, and the number and severity of skin lesions. Patients were requested to report their symptoms of pruritus, burning, or discomfort on a scale of 1 to 10. Severity of skin lesions was evaluated as percent improvement compared to initial start of venlafaxine therapy. Fourteen patients reported good compliance with the treatment for 3-6 months. One patient discontinued venlafaxine within 1 week due to excessive nausea. Following 1 month of treatment, a significant improvement in psychiatric and skin symptoms, and the number and severity of skin lesions was detected. The average reported pruritus/discomfort score improved from 8.5/10 to 2.8/10. An average 45% reduction in skin lesions was noted after 4 weeks of therapy. After 12 weeks of therapy, continued improvement of symptoms and skin lesions was observed, with a 75% average reduction in skin lesions. Improvements were maintained after 6 months of treatment, at which time the dose of venlafaxine was reduced to a maintenance dose of 37.5 mg per day, 37.5 mg every other day, or discontinued if the patient was free of symptoms. Venlafaxine has a low affinity for muscarinic, histaminergic, and alpha1-andergenic receptors, and its side-effect profile is low.
P35 STRESSFUL MAJOR LIFE EVENTS ARE ASSOCIATED WITH A HIGHER PREVALENCE OF CUTANEOUS SENSORY SYMPTOMS Madhulika A Gupta, MD, Univ of Western Ontario, Dept. of Psychiatry, London, ON, Canada, Aditya Gupta, MD, PhD, Univ of Western Ontario, Dept. of Psychiatry, London, ON, Canada Background: Psychological stress resulting from stressful major life events are known to exacerbate a wide range of skin disorders. Objective: Examine the relation between stressful major life events and dermatologic symptoms among a non-clinical sample. Design: Cross-sectional survey. Setting: Community-based subjects from London, Ontario, Canada were recruited from the local university, schools and churches. Participants: Out of 600 consecutive, consenting volunteers 316 subjects(73 men and 243 women; mean ⫾ SD age: 38.7 ⫾ 14.8 years; marital status: 54% married; race: 94% ‘white’) completed the survey for this study. Exclusion criteria were history of a major dermatologic or medical disorder. Main outcome measure: Number of major life events experienced over the previous 6 months measured using the Social Readjustment Rating Scale of Holmes and Rahe, and the frequency and severity of a range of cutaneous symptoms(‘burning’, ‘crawling sensation’, ‘tingling’, ‘pricking’ or ‘pins and needles’, ‘pain’, ‘tenderness’ of skin, ‘numbness’, ‘moderate to severe itching’, and ‘easy bruising’) that the subject may have experienced over the previous 1 month. Results: The most frequently reported body region affected was the scalp (59.5%) and the most frequently reported symptom was itching (69.3%). The total number of major life events experienced over the previous 6 months correlated with the severity of the individual cutaneous symptoms (0.22 Pearson r 0.41, p⬍0.001), and the total cutaneous symptom severity score(sum of all cutaneous severity ratings)(Pearson r ⫽ 0.40, p⬍0.001). This correlation remained significant after the possible confounding effect of psychological factors on cutaneous symptoms was partialled out statistically (partial r ⫽ 0.19, p ⫽ 0.001). Discussion: We observed a direct correlation between the number of major life events experienced over the previous 6 months and cutaneous symptoms experienced over the previous 1 month by non-clinical subjects. The correlation remained significant after the effect of psychological factors was partialled out, suggesting that this relation holds even if the subject does not acknowledge psychological distress in reaction to the major life event. Disclosure not available at press time.
Disclosure not available at press time.
P34 INTRAVENOUS IMMUNOGLOBULIN THERAPY: EFFECTIVE IN SKIN DISEASE? A RETROSPECTIVE REVIEW OF MAYO CLINIC EXPERIENCE Davis A. Wetter, Mayo Clinic/Mayo Foundation, Rochester, MN, United States, Mark Davis, MD, Mayo Clinic/Mayo Foundation, Rochester, MN, United States, James Yiannias, MD, Mayo Clinic, Scottsdale, Scottsdale, AZ, United States, Mark Dahl, MD, Mayo Clinic, Scottsdale, Scottsdale, AZ, United States Background: Recent literature reports intravenous immunoglobulin (IVIg) as an effective treatment for a variety of skin diseases, most notably immunobullous disease refractory to conventional immunosuppressive therapy. Our anecdotal experience with IVIg has been less favorable than published studies. Objective: To examine the use and effectiveness of IVIg treatment for skin disease at Mayo Clinic. Methods: Patients who had received IVIg for skin disease between 1996 and 2003 at Mayo Clinic were identified. The following information was sought: disease duration and severity, previous immunosuppressive regimens, IVIg administration protocol, concomitant therapy, and response to IVIg treatment. In addition to comparing patients’ symptoms and signs before and after therapy, pertinent lab tests and fluctuations in concomitant immunosuppressive doses needed to control disease were used as surrogate indices of treatment efficacy. Results: 19 patients with skin disease were treated with IVIg: immunobullous disease [11 patients (pemphigus vulgaris (7) bullous pemphigoid (3) and cicatrical pemphigoid (1))]; dermatomyositis (2); mixed connective tissue disease (1); chronic urticaria (1); scleromyxedema (1); leukocytoclastic vasculitis (1); linear IgA bullous disease (1); and toxic epidermal necrolysis (1). Responses of each disease were as follows: pemphigus vulgaris (1 PR, 6 NR); bullous pemphigoid (1 CR, 3 NR); dermatomyositis (1 CR, 1 PR); mixed connective tissue disease (1 CR); chronic urticaria (1 CR); scleromyxedema (1 CR); leukocytoclastic vasculitis (1 PR); linear IgA bullous disease (1 CR); and toxic epidermal necrolysis (1 NR). Overall, 10 of the 19 patients (53%) experienced no clinical response to IVIg therapy. 6 patients (31%) experienced a complete clinical response, while 3 patients (16%) exhibited a partial response. 9 of the 11 patients (82%) with autoimmune bullous disease experienced no clinical response. Non-responders received an average of 7 treatment cycles (ranging from 5 to 11) at a dose of 2g/kg per monthly cycle. Side effects from IVIg were mild and included headache, nausea, and myalgias. Discussion: Although the present study is a retrospective study of a small and heterogenous group, IVIg was effective in less than half of the patients with skin disease, and in particular, was not effective in the majority of the patients with autoimmune bullous disease. Conclusion: Our experience of IVIg for skin disease is less favorable than that reported in the literature. Further studies are needed to verify the efficacy of IVIg for skin disease.
MUTATIONS IN FUMARATE HYDRATASE CAUSE HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CARCINOMA IN FAMILIES IN NORTH AMERICA Toro R Jorge, MD, NCI, Washigton, DC, United States, Berton Zbar, MD, NCI, Washigton, DC, United States, Maria Turner, MD, NCI, Washigton, DC, United States, Marston Linehan, MD, NCI, Washigton, DC, United States Hereditary leiomyomatosis and renal cell cancer (HLRCC) (OMIM 605839) is an autosomal dominant disorder characterized by smooth muscle tumors of the skin and uterus and/or renal cancer. Although the identification of germline mutations in fumarate hydratase (FH) in European families supports FH as the susceptibility gene for HLRCC, its role in North American families has not been studied. We screened for germline mutations in FH in 35 North American families with cutaneous leiomyomas. Sequence analysis revealed mutations in FH in 31 families (88%). Twenty different mutations in FH gene were identidied, of which 18 were novel. Of these 20 mutations, 2 were insertions and 5 were deletions that caused frameshifts leading to premature truncation of the protein, and 13 were missense mutations. Eleven unrelated families shared a common mutation: R190H. Eighty-one individuals (47 women and 34 men) had cutaneous leiomyomas. Ninety-eight percent (46/47) of women with cutaneous leiomyomas also had uterine fibroids. Eighty-nine percent (41/46) of women with leiomyomas and uterine fibroids had a total hysterectomy, 44% by the age of 30 years. We identified 13 individuals in 5 families with unilateral and solitary renal tumors. Six individuals from 4 families had papillary type II renal cell carcinoma and one individual from one family had collecting duct renal cell carcinoma. Our study shows that mutations in FH are associated with HLRCC in North American families. HLRCC is associated with clinically significant uterine fibroids and aggressive renal tumors. Our study expands the histologic spectrum of renal tumors and mutations in FH associated with HLRCC.
Disclosure not available at press time.
Disclosure not available at press time.
MARCH 2004
P36
J AM ACAD DERMATOL
P9
P35 STRESSFUL MAJOR LIFE EVENTS ARE ASSOCIATED WITH A HIGHER PREVALENCE OF CUTANEOUS SENSORY SYMPTOMS Madhulika A Gupta, MD, Univ of Western Ontario, Dept. of Psychiatry, London, ON, Canada, Aditya Gupta, MD, PhD, Univ of Western Ontario, Dept. of Psychiatry, London, ON, Canada Background: Psychological stress resulting from stressful major life events are known to exacerbate a wide range of skin disorders. Objective: Examine the relation between stressful major life events and dermatologic symptoms among a non-clinical sample. Design: Cross-sectional survey. Setting: Community-based subjects from London, Ontario, Canada were recruited from the local university, schools and churches. Participants: Out of 600 consecutive, consenting volunteers 316 subjects(73 men and 243 women; mean ⫾ SD age: 38.7 ⫾ 14.8 years; marital status: 54% married; race: 94% ‘white’) completed the survey for this study. Exclusion criteria were history of a major dermatologic or medical disorder. Main outcome measure: Number of major life events experienced over the previous 6 months measured using the Social Readjustment Rating Scale of Holmes and Rahe, and the frequency and severity of a range of cutaneous symptoms(‘burning’, ‘crawling sensation’, ‘tingling’, ‘pricking’ or ‘pins and needles’, ‘pain’, ‘tenderness’ of skin, ‘numbness’, ‘moderate to severe itching’, and ‘easy bruising’) that the subject may have experienced over the previous 1 month. Results: The most frequently reported body region affected was the scalp (59.5%) and the most frequently reported symptom was itching (69.3%). The total number of major life events experienced over the previous 6 months correlated with the severity of the individual cutaneous symptoms (0.22 Pearson r 0.41, p⬍0.001), and the total cutaneous symptom severity score(sum of all cutaneous severity ratings)(Pearson r ⫽ 0.40, p⬍0.001). This correlation remained significant after the possible confounding effect of psychological factors on cutaneous symptoms was partialled out statistically (partial r ⫽ 0.19, p ⫽ 0.001). Discussion: We observed a direct correlation between the number of major life events experienced over the previous 6 months and cutaneous symptoms experienced over the previous 1 month by non-clinical subjects. The correlation remained significant after the effect of psychological factors was partialled out, suggesting that this relation holds even if the subject does not acknowledge psychological distress in reaction to the major life event. Disclosure not available at press time.
Disclosure not available at press time.
P34 INTRAVENOUS IMMUNOGLOBULIN THERAPY: EFFECTIVE IN SKIN DISEASE? A RETROSPECTIVE REVIEW OF MAYO CLINIC EXPERIENCE Davis A. Wetter, Mayo Clinic/Mayo Foundation, Rochester, MN, United States, Mark Davis, MD, Mayo Clinic/Mayo Foundation, Rochester, MN, United States, James Yiannias, MD, Mayo Clinic, Scottsdale, Scottsdale, AZ, United States, Mark Dahl, MD, Mayo Clinic, Scottsdale, Scottsdale, AZ, United States Background: Recent literature reports intravenous immunoglobulin (IVIg) as an effective treatment for a variety of skin diseases, most notably immunobullous disease refractory to conventional immunosuppressive therapy. Our anecdotal experience with IVIg has been less favorable than published studies. Objective: To examine the use and effectiveness of IVIg treatment for skin disease at Mayo Clinic. Methods: Patients who had received IVIg for skin disease between 1996 and 2003 at Mayo Clinic were identified. The following information was sought: disease duration and severity, previous immunosuppressive regimens, IVIg administration protocol, concomitant therapy, and response to IVIg treatment. In addition to comparing patients’ symptoms and signs before and after therapy, pertinent lab tests and fluctuations in concomitant immunosuppressive doses needed to control disease were used as surrogate indices of treatment efficacy. Results: 19 patients with skin disease were treated with IVIg: immunobullous disease [11 patients (pemphigus vulgaris (7) bullous pemphigoid (3) and cicatrical pemphigoid (1))]; dermatomyositis (2); mixed connective tissue disease (1); chronic urticaria (1); scleromyxedema (1); leukocytoclastic vasculitis (1); linear IgA bullous disease (1); and toxic epidermal necrolysis (1). Responses of each disease were as follows: pemphigus vulgaris (1 PR, 6 NR); bullous pemphigoid (1 CR, 3 NR); dermatomyositis (1 CR, 1 PR); mixed connective tissue disease (1 CR); chronic urticaria (1 CR); scleromyxedema (1 CR); leukocytoclastic vasculitis (1 PR); linear IgA bullous disease (1 CR); and toxic epidermal necrolysis (1 NR). Overall, 10 of the 19 patients (53%) experienced no clinical response to IVIg therapy. 6 patients (31%) experienced a complete clinical response, while 3 patients (16%) exhibited a partial response. 9 of the 11 patients (82%) with autoimmune bullous disease experienced no clinical response. Non-responders received an average of 7 treatment cycles (ranging from 5 to 11) at a dose of 2g/kg per monthly cycle. Side effects from IVIg were mild and included headache, nausea, and myalgias. Discussion: Although the present study is a retrospective study of a small and heterogenous group, IVIg was effective in less than half of the patients with skin disease, and in particular, was not effective in the majority of the patients with autoimmune bullous disease. Conclusion: Our experience of IVIg for skin disease is less favorable than that reported in the literature. Further studies are needed to verify the efficacy of IVIg for skin disease.
MUTATIONS IN FUMARATE HYDRATASE CAUSE HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CARCINOMA IN FAMILIES IN NORTH AMERICA Toro R Jorge, MD, NCI, Washigton, DC, United States, Berton Zbar, MD, NCI, Washigton, DC, United States, Maria Turner, MD, NCI, Washigton, DC, United States, Marston Linehan, MD, NCI, Washigton, DC, United States Hereditary leiomyomatosis and renal cell cancer (HLRCC) (OMIM 605839) is an autosomal dominant disorder characterized by smooth muscle tumors of the skin and uterus and/or renal cancer. Although the identification of germline mutations in fumarate hydratase (FH) in European families supports FH as the susceptibility gene for HLRCC, its role in North American families has not been studied. We screened for germline mutations in FH in 35 North American families with cutaneous leiomyomas. Sequence analysis revealed mutations in FH in 31 families (88%). Twenty different mutations in FH gene were identidied, of which 18 were novel. Of these 20 mutations, 2 were insertions and 5 were deletions that caused frameshifts leading to premature truncation of the protein, and 13 were missense mutations. Eleven unrelated families shared a common mutation: R190H. Eighty-one individuals (47 women and 34 men) had cutaneous leiomyomas. Ninety-eight percent (46/47) of women with cutaneous leiomyomas also had uterine fibroids. Eighty-nine percent (41/46) of women with leiomyomas and uterine fibroids had a total hysterectomy, 44% by the age of 30 years. We identified 13 individuals in 5 families with unilateral and solitary renal tumors. Six individuals from 4 families had papillary type II renal cell carcinoma and one individual from one family had collecting duct renal cell carcinoma. Our study shows that mutations in FH are associated with HLRCC in North American families. HLRCC is associated with clinically significant uterine fibroids and aggressive renal tumors. Our study expands the histologic spectrum of renal tumors and mutations in FH associated with HLRCC.
Disclosure not available at press time.
Disclosure not available at press time.
MARCH 2004
P36
J AM ACAD DERMATOL
P9