Reduced risk of suicidal behaviours associated with the treatment of hidradenitis suppurativa with tumour necrosis factor alpha antagonists: results from the US FDA Adverse Events Reporting System pharmacovigilance database.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent condition that presents as painful, suppurating lesions in the apocrine gland-bearing skin regions. HS has been associated with increased suicidal behaviours (SB), independent of any treatment. TNF-alpha antagonists are used to treat moderate-to-severe HS and have also been associated with SB, a factor that could confound the decision to use the TNF-α antagonists in the moderately to severely affected HS patients, who may already be experiencing increased SB risk. OBJECTIVES: To determine presence or absence of a safety signal for SB when HS is treated with TNF-α antagonists. METHODS: We calculated the reporting odds ratios (ROR) with 95% CI of SB associated with treatment for HS with TNF-α antagonists vs. the reference group of all other treatments for HS in the US Food and Drug Administration pharmacovigilance database from 1 January 2004 to 31 March 2019. A second analysis excluded isotretinoin (which has been used to treat HS and has also been associated with SB) from the reference group. RESULTS: There was a signal for decreased risk of SB with TNF-α antagonists (ROR = 0.1959, 95% CI 0.1247-0.3079; z = 7.071, P < 0.0001] vs. all other HS treatments; the ROR did not change significantly after isotretinoin was excluded from the reference group. CONCLUSIONS: Treatment of HS with TNF-α antagonists is associated with a decreased risk of SB.

Assessing dutasteride-associated sexual dysfunction using the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Incidences of sexual dysfunction due to the use of 5 α-reductase inhibitors have been suggested. Despite low sexual dysfunction reported in clinical trials, an analysis of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database revealed a significant disproportionality in the reporting of sexual dysfunction with the use of finasteride. Therefore, it is likely that a similar relationship with dutasteride may exist. OBJECTIVE: To determine whether dutasteride use leads to a higher risk of sexual dysfunction compared to a baseline risk for all other drugs using the FAERS database. METHODS: A case by non-case disproportionality approach was used whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. Cases of dutasteride-associated sexual dysfunction were compared to a reference risk of sexual dysfunction for all other drugs in the database. RESULTS: A significant disproportionality in reporting of sexual dysfunction with the use of dutasteride was observed. The disproportionality was present for all age ranges except for 31-45 years where there were few overall reports of adverse events. LIMITATIONS: Adverse events can be underreported, and selection bias is inherent in the FAERS. CONCLUSION: Dutasteride use is associated with an increase in reports of sexual dysfunction.

Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey--Outpatient Department data collected by the U.S. National Center for Health Statistics from 1995 to 2002.

BACKGROUND: Psychogenic factors have been considered to be important in the exacerbation and possibly the onset of rosacea. However, there are very few studies that have reported conclusive findings. OBJECTIVES: To examine the association between rosacea and major depressive disease, a common and usually treatable psychiatric disorder. METHODS: Data from 1995 to 2002, collected by the National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Care Survey, which are both nationally representative surveys of healthcare visits in the U.S.A., were studied. The basic sampling unit in both surveys is the patient visit or encounter. A "Rosacea" variable was created by grouping all rosacea (ICD-9-CM code 695.3) visits and a "Depression" variable was created by grouping the patient visits related to major depressive disorder (ICD-9-CM codes 296.2, 296.3 and 311). As alcohol abuse has been implicated in rosacea, and alcohol can confound symptoms of depression, an "Alcohol" variable was created by grouping all ICD-9-CM codes related to alcohol dependence and abuse (codes 303, 303.0, 303.9 and 305.0). All analyses were conducted using the Complex Samples module of SPSS version 13, to account for the multistage probability sampling design used to collect the data. RESULTS: The weighted data were representative of over 608 million dermatology visits between 1995 and 2002. Logistic regression analysis using "Rosacea" as the dependent variable and age, sex, "Alcohol" and "Depression" as independent variables revealed that the odds ratio for depressive disease in the rosacea group was 4.81 (95% confidence interval 1.39-16.62). The association between "Alcohol" and "Rosacea" was not significant. CONCLUSIONS: The comorbidity between major depressive disease and rosacea may have important clinical implications. Alcohol abuse does not appear to play a significant role in this association.

Stressful major life events are associated with a higher frequency of cutaneous sensory symptoms: an empirical study of non-clinical subjects.

BACKGROUND: Psychological stress resulting from stressful major life events is known to exacerbate a wide range of skin disorders. OBJECTIVE: To examine the relationship between stressful major life events and dermatological symptoms among a non-clinical sample. DESIGN: A 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; age 38.7 +/- 14.8 (mean +/- SD) years; marital status 54% married; race 94%'white'] completed the survey for this study. The exclusion criterion was a history of a major dermatological or medical disorder. MAIN OUTCOME MEASURE: The number of major life events experienced over the previous 6 months measured using the Social Readjustment Rating Scale (SRRS) 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 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 < or = Pearson r < or = 0.41, P < 0.001) and with 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 relationship holds even if the subject does not acknowledge psychological distress in reaction to the major life event.

Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation.

OBJECTIVE: The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD. METHOD: Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength. RESULTS: PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects. CONCLUSIONS: The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.

Dissatisfaction with skin appearance among patients with eating disorders and non-clinical controls.

BACKGROUND: We have recently observed that women with the eating disorders (EDs) anorexia nervosa and bulimia nervosa report a significantly greater (P = 0.002) dissatisfaction with the appearance of their skin than do non-clinical controls. OBJECTIVES: To examine further the nature of the dissatisfaction with skin appearance in women with EDs. METHODS: Several psychosocial and body image parameters, including whether or not the subjects were satisfied with a wide range of attributes associated with non-diseased skin, were surveyed in women aged < or = 30 years. Survey data from 32 women with EDs and 34 randomly selected community-based non-clinical controls were examined. RESULTS: Eighty-one per cent of the patients with EDs vs. 56% of the controls reported dissatisfaction with the appearance of their skin (P = 0.03), particularly with respect to its dryness and roughness. Other attributes that were rated more frequently were 'bags' and 'darkness' under the eyes, freckles, fine wrinkles and patchy hyperpigmentation. CONCLUSIONS: There is a high prevalence of dissatisfaction with skin appearance among women aged < or = 30 years, which is even higher among patients with EDs.

Antidepressant drugs in dermatology.

Antidepressant drugs can be an important component of the dermatologists' therapeutic armamentarium. When considering the use of psychotropic agents in dermatology two major factors should be considered: (1) the accurate diagnosis of the comorbid psychiatric disorder, and (2) the presence of proper indications for the use of antidepressant agents. Antidepressant drugs are used in the management of the psychiatric syndromes, which are most frequently comorbid with dermatologic disorders, i.e., Major Depressive Disorder, Obsessive-Compulsive Disorder, Body Dysmorphic Disorder, Post-traumatic Stress Disorder and Social Phobia. The antihistaminic and analgesic properties of some antidepressants such as doxepin and amitriptyline, are also of benefit in the treatment of some pruritic and neuralgic states. The specific guidelines, side effect profile, drug-drug interactions, and the most current indications should always be obtained for any particular antidepressant agent before it is prescribed.

Weight-related body image concerns among 18-24-year-old women in Canada and India: an empirical comparative study.

OBJECTIVE: Sociocultural factors are important in the pathogenesis of eating disorders. We examined some core (DSM IV) features of eating disorders, i.e., drive for thinness and dissatisfaction with the weight of the abdomen, hips, and thighs among women in Canada and India. METHODS: A total of 65 Canadian (mean+/-S.D. age: 21.4+/-2.0 years) and 47 Indian (mean+/-S.D. age: 18.7+/-4.1 years) women completed the Drive for Thinness (DT) and Body Dissatisfaction (BD) subscales of the Eating Disorder Inventory (EDI) and in addition rated the degree to which they believed all major regions of their body were overweight. RESULTS: After the effects of body mass index (BMI) were partialled out statistically, the DT (EDI) and BD (EDI) scores were not significantly different between the two countries. In both groups, concerns about the weight of the abdomen, hips, thighs, and legs loaded on a factor that essentially described the 'body dissatisfaction' construct. After the effects of BMI were partialled out, however, the factor scores from this factor correlated with BD (EDI) in the Canadian but not the Indian sample. DISCUSSION: In contrast to the Canadian women, the Indian women did not overestimate the 'fatness' of their abdomen, hips, thighs, and legs. Among the Indian women, concerns about the weight of the upper torso (i.e., face, neck, shoulders, and chest) emerged as a distinct body image construct. In conclusion, after the effect of BMI was controlled for statistically, the Canadian and Indian women scored similarly on some of the core features of eating disorders, as measured by the DT (EDI) and BD (EDI) subscales, however, the nature of the underlying body image construct was different between the two groups.

Olanzapine may be an effective adjunctive therapy in the management of acne excoriée: a case report.

BACKGROUND: The self-inflicted dermatoses such as acne excorieé and neurotic excoriations are often chronic, recurring, and resistant to standard dermatologic therapies. OBJECTIVE: We present a 28-year-old woman with longstanding acne excorieé, whose acne started at age 14 years and was followed by acne excorieé at age 16 years. The patient reported that her acne and self-excoriative behavior were exacerbated by psychological stress. The previously treatment-resistant acne excorieé responded favorably to treatment with the atypical antipsychotic agent olanzapine. METHODS: The patient was started on olanzapine 2.5 mg at bedtime. RESULTS: After 4 weeks of therapy with olanzapine she reported a significant decline in her self-excoriative behavior which was associated with an improvement in her acne excorieé. The patient used the olanzapine 2.5 mg for 6 months, during which time she also entered psychotherapy in order to deal with some psychosocial stressors that were exacerbating her self-excoriative behavior. The patient has not experienced a recurrence in her self-excoriative behavior or acne excorieé for 4 months after discontinuing the olanzapine. CONCLUSION: Olanzapine may prove to be a useful adjunctive therapy in some self-induced dermatoses including acne excorieé.

The use of antidepressant drugs in dermatology.

This paper provides an updated review of the use of antidepressant drugs in dermatology. Some of the psychiatric disorders that are usually comorbid with dermatological disorders and respond to antidepressants include major depressive disorder, obsessive compulsive disorder, body dysmorphic disorder, social phobia and post-traumatic stress disorder usually secondary to trauma and abuse during early life. Cutaneous symptoms may be the feature of a primary psychiatric disorder, e.g. cutaneous body image problems, dermatitis artefacta, neurotic excoriations and trichotillomania, or psychiatric syndromes may be comorbid with a primary dermatological disorder such as the association of major depressive disorder or social phobia with psoriasis and obsessive compulsive disorder with acne excoriee. Some of the salient pharmacological properties of the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) antidepressants are reviewed. The review indicates that the SSRI antidepressants are potentially beneficial in the management of all the major psychiatric syndromes that are encountered in dermatological disorders. The generally more favourable side-effect profile of the SSRIs, such as lower cardiotoxicity in contrast to the TCAs, has made them the first-line agents for the treatment of depression. Furthermore, some of the pharmacological properties of the antidepressant agents that are not related to their antidepressant activity, such as the histamine H1 blocking effect of TCAs, such as doxepin, amitriptyline and trimipramine, are of benefit in dermatological conditions such as urticaria and pruritus. This paper reviews the general guidelines for use of antidepressants and salient drug-drug interactions resulting mainly from the inhibition of the cytochrome P450 (CYP) 2D6 and 3A3/4 isoenzymes by some of the SSRI antidepressants. Before prescribing an antidepressant agent, the specific guidelines, side-effect profile, drug-drug interactions and most current indications should always be obtained.

The use of psychotropic drugs in dermatology.

In approximately one third of dermatology patients, the effective management of a skin condition also involves consideration of associated emotional and psychosocial factors. Psychotropic drugs are an important part of the dermatologist's therapeutic armamentarium. This article reviews some of the salient pharmacologic guidelines and important drug-drug interactions involved in the use of the major classes of, for example, antidepressants and antipsychotic drugs, in the dermatologic patient.

Epidemiology and prevalence of onychomycosis in HIV-positive individuals.

BACKGROUND: Patients who are human immunodeficiency virus (HIV) positive are predisposed to the development of infections including tinea pedis and onychomycosis. While smaller studies have been reported, there has been no large study evaluating the prevalence of onychomycosis in HIV-positive individuals, or comparing the development of onychomycosis in a typical temperate area with that in a typical tropical area. METHODS: HIV-positive individuals were evaluated at five clinics: four in Ontario, Canada and one in Sao Paulo, Brazil. The subjects were asked questions to determine the epidemiology of onychomycosis in HIV-positive individuals. The feet were examined and nail material was obtained for mycologic examination to determine the causative organism of onychomycosis. RESULTS: A total of 500 subjects were examined (415 men and 85 women; age (mean +/- SE), 39 +/- 0.4 years; 400 Canadian, 100 Brazilian). The racial origins of the Canadian patients were: Caucasian, 83.8%; Asian, 4.3%; African-American, 8.1%; Hispanic, 3.3%; American Indian, 0.3%. The Brazilian origins were: Caucasian, 68.7%; African, 18.1%; mixed race, 13.3%. Abnormal appearing nails and mycologic evidence of onychomycosis were present in 200 (40.0%) and 116 (23.2%), respectively, of 500 subjects. The prevalence of onychomycosis in the Canadian and Brazilian samples was 24.0% (96 of 400) and 20.0% (20 of 100), respectively. The projected prevalence of onychomycosis in HIV-positive individuals in Canada was 19.9% (95% CI: 16.0-23.9%) after taking into account the age and sex distribution of HIV-positive individuals in the population. When nails appeared clinically abnormal, the prevalence of onychomycosis was 50.5% (Canada, 51.3%; Brazil, 45.5%). For comparison, published data indicate that the prevalence of onychomycosis in immunocompetent individuals living in Canada is 6.9%. The clinical presentation of onychomycosis for the whole sample (n=500) was: distal and lateral subungual onychomycosis (DLSO), 20.0%; white superficial onychomycosis (WSO), 3.6%; proximal subungual onychomycosis (PSO), 1.8% (Canadian and Brazilian samples: DLSO 21.2% vs. 15.0%, WSO 3.3% vs. 5.0%, and PSO 1.5% vs. 3.0%). The distribution of the causative fungal organisms was: dermatophytes: Candida species: nondermatophyte molds, 73:2:2 (Canadian and Brazilian samples: dermatophytes 95.5% vs. 90.9%, Candida species 3.0% vs. 0%, and nondermatophyte molds 1.5% vs. 9.0%). The use of protease inhibitors, reverse transcriptase inhibitors, or oral antifungal agents did not make a significant difference in the prevalence of onychomycosis for both the Canadian and Brazilian groups. Patients with onychomycosis were aware of their abnormal appearing nails (chi2(1)=69.7, P<0.001), embarrassed by the appearance of their nails (chi2(1)=29.7, P<0.001), and took measures to hide their nails from other individuals. A higher proportion of individuals with onychomycosis experienced discomfort compared with those without the disease (chi2(1)=9.0, P=0.003). Also, individuals who experienced pain in the nail unit were more likely to have onychomycosis (risk odds ratio (ROR), 2.2; 95% CI: 1.0-4.7, P=0.05). CONCLUSIONS: The prevalence of onychomycosis in HIV-positive individuals in the sample of 500 patients was 23.2%. In the Canadian (n=400) and Brazilian (n=100) samples, the corresponding figures were 24% and 20%, respectively, with the predominant causative organisms being dermatophytes. The projected prevalence of onychomycosis in HIV-positive Canadians is 19.9%. Predisposing factors include a CD4 count of approximately 370, a positive family history of onychomycosis, a history of tinea pedis, and walking barefoot around pools. Onychomycosis can be symptomatic, a source of embarrassment, and a potential cause of morbidity.

Herpes zoster in the medically healthy child and covert severe child abuse.

Herpes zoster is associated with depressed cell-mediated immunity and occurs rarely in the medically healthy nonimmunocompromised child. We report 4 cases of childhood-onset herpes zoster in the absence of a medical disorder. All 4 patients reported experiencing severe, chronic child abuse when the herpes zoster first appeared. It is possible that the severe chronic psychologic stress resulting from the abuse depressed the patients' cell-mediated immune status and thereby predisposed them to herpes zoster. Our findings suggest that the clinician's suspicion should be heightened for the possibility of covert child abuse and secondary stress when managing an otherwise apparently healthy child with herpes zoster.

Olanzapine is effective in the management of some self-induced dermatoses: three case reports.

Self-inflicted dermatoses are often difficult to treat. We present three patients with excoriated acne, self-induced skin ulcers, and trichotillomania, respectively, whose symptoms responded favorably to a 2- to 4-week course of the atypical antipsychotic olanazpine at a dosage of 2.5 to 5.0 mg daily. In two of three patients, the efficacy of the olanzapine was most likely related to an attenuation of dissociative symptoms that were associated with the self-induced skin ulcers and trichotillomania.

Nonweight-related body image concerns among female eating-disordered patients and nonclinical controls: some preliminary observations.

OBJECTIVE: Eating disorders(ED) have been classically associated with a concern about body shape and size that manifests mainly as an intense fear of weight gain (DSM-IV criteria). To further examine the nature of the body image disturbance in ED, we surveyed the prevalence of nonweight-related body image concerns among ED patients and nonclinical controls. METHOD: We examined 53 women (M +/- SD age: 28.1 +/- 6.8 years) with anorexia nervosa and/or bulimia nervosa (DSM-III-R criteria) and 73 randomly selected nonclinical women (M +/- SD age: 30.2 +/- 6.6 years) from the community. The participants rated (by checking a "Yes" or "No") whether they were satisfied with the appearance of the following body regions: their skin, teeth, jaw, nose, eyes, ears, hair, and height and completed the Drive for Thinness (DT) and Body Dissatisfaction (BD) subscales of the Eating Disorders Inventory (EDI). RESULTS: The frequencies of dissatisfaction with the appearance of various physical attributes among the ED patients versus the nonclinical controls were as follows: skin: 79.2% vs. 52.1%, p =.002; teeth: 62.3% vs. 39.7%, p =. 012; jaw: 24.5% vs. 9.7%, p =.026; nose: 45.3% vs. 24.7%, p =.015; eyes: 22.6% vs. 12.3%, p =.12; ears: 20.8% vs. 2.7%, p =.001; hair: 52.8% vs. 39.7%, p =.14; and height: 28.3% vs. 13.7%, p =.04. As expected, the M +/- SD DT (EDI): 14.0 +/- 6.1 vs.3.5 +/- 4.6, p <. 0001 and the M +/- SD BD (EDI): 19.7 +/- 5.8 vs. 10.1 +/- 7.3, p <. 0001, were both higher in the ED group. Furthermore, greater dissatisfaction with nonweight-related body image was associated with higher DT and BD scores. CONCLUSION: The higher prevalence of dissatisfaction with appearance of most of the nonweight-related physical attributes is probably an indication of the core ego deficits that are often present in ED and an index of the severity of the overall body image disturbance in these patients, and not indicative of another condition (e.g., body dysmorphic disorder) as the current nosology (DSM-IV) suggests.