Efficacy of Roflumilast Foam, 0.3%, in Patients With Seborrheic Dermatitis: A Double-blind, Vehicle-Controlled Phase 2a Randomized Clinical Trial.

Importance: Current topical treatment options for seborrheic dermatitis are limited by efficacy and/or safety. Objective: To assess safety and efficacy of roflumilast foam, 0.3%, in adult patients with seborrheic dermatitis affecting the scalp, face, and/or trunk. Design, Setting, and Participants: This multicenter (24 sites in the US and Canada) phase 2a, parallel group, double-blind, vehicle-controlled clinical trial was conducted between November 12, 2019, and August 21, 2020. Participants were adult (aged ≥18 years) patients with a clinical diagnosis of seborrheic dermatitis for a 3-month or longer duration and Investigator Global Assessment (IGA) score of 3 or greater (at least moderate), affecting 20% or less body surface area, including scalp, face, trunk, and/or intertriginous areas. Data analysis was performed from September to October 2020. Interventions: Once-daily roflumilast foam, 0.3% (n = 154), or vehicle foam (n = 72) for 8 weeks. Main Outcomes and Measures: The main outcome was IGA success, defined as achievement of IGA score of clear or almost clear plus 2-grade improvement from baseline, at week 8. Secondary outcomes included IGA success at weeks 2 and 4; achievement of erythema score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; achievement of scaling score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; change in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline; and WI-NRS success, defined as achievement of 4-point or greater WI-NRS score improvement in patients with baseline WI-NRS score of 4 or greater. Safety and tolerability were also assessed. Results: A total of 226 patients (mean [SD] age, 44.9 [16.8] years; 116 men, 110 women) were randomized to roflumilast foam (n = 154) or vehicle foam (n = 72). At week 8, 104 (73.8%) roflumilast-treated patients achieved IGA success compared with 27 (40.9%) in the vehicle group (P < .001). Roflumilast-treated patients had statistically significantly higher rates of IGA success vs vehicle at week 2, the first time point assessed. Mean (SD) reductions (improvements) on the WI-NRS at week 8 were 59.3% (52.5%) vs 36.6% (42.2%) in the roflumilast and vehicle groups, respectively (P < .001). Roflumilast was well tolerated, with the rate of adverse events similar to that of the vehicle foam. Conclusions and Relevance: The results from this phase 2a randomized clinical trial of once-daily roflumilast foam, 0.3%, demonstrated favorable efficacy, safety, and local tolerability in the treatment of erythema, scaling, and itch caused by seborrheic dermatitis, supporting further investigation as a nonsteroidal topical treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04091646.

Cuero cabelludo sensible: diagnóstico y manejo práctico / Sensitive Scalp: Diagnosis and Practical Management

El cuero cabelludo sensible es una piel sensible de localización especial. Puede ser primario, cuando se presenta sin enfermedad del cuero cabelludo, y secundario cuando es atribuible a procesos como psoriasis, dermatitis seborreica, dermatitis atópica y otros. Las manifestaciones clínicas de la forma primaria son subjetivas. El escozor, picor, tricodinia y sensaciones disestésicas son el motivo de consulta, muy a menudo coincidiendo con alopecia. Clínicamente la piel del cuero cabelludo puede ser normal o eritematosa. No hay datos de laboratorio o histológicos específicos para un diagnóstico objetivo. Los factores desencadenantes son endógenos como el estrés y alteraciones emocionales y psicopatológicas, o ambientales como los tópicos inadecuados y los cosméticos. El tratamiento debe ser personalizado, incluyendo pimecrólimus, la hidratación con ácido hialurónico, y la mesoterapia con plasma rico en factores de crecimiento (AU)

Sensitive scalp is sensitive skin located on the scalp. Sensitivity is considered primary in the absence of an associated scalp disorder and secondary when caused by conditions such as psoriasis, seborrheic dermatitis, and atopic dermatitis. The clinical manifestations of primary sensitive scalp are subjective. Common presenting symptoms are burning, itching, trichodynia, and dysesthesia, often coinciding with hair loss. Clinically, the skin appears normal or red. An objective diagnosis based on laboratory or histologic findings is not possible. Triggers may be endogenous (e.g., stress and emotional or psychopathological disturbances) or exogeneous (e.g., topical products and cosmetics). Treatment must be individualized. Options include pimecrolimus, hydration with hyaluronic acid, and mesotherapy with plasma rich in growth factors (AU)

[Translated article] Sensitive Scalp: Diagnosis and Practical Management / Cuero cabelludo sensible: diagnóstico y manejo práctico

Sensitive scalp is sensitive skin located on the scalp. Sensitivity is considered primary in the absence of an associated scalp disorder and secondary when caused by conditions such as psoriasis, seborrheic dermatitis, and atopic dermatitis. The clinical manifestations of primary sensitive scalp are subjective. Common presenting symptoms are burning, itching, trichodynia, and dysesthesia, often coinciding with hair loss. Clinically, the skin appears normal or red. An objective diagnosis based on laboratory or histologic findings is not possible. Triggers may be endogenous (e.g., stress and emotional or psychopathological disturbances) or exogeneous (e.g., topical products and cosmetics). Treatment must be individualized. Options include pimecrolimus, hydration with hyaluronic acid, and mesotherapy with plasma rich in growth factors (AU)

El cuero cabelludo sensible es una piel sensible de localización especial. Puede ser primario, cuando se presenta sin enfermedad del cuero cabelludo, y secundario cuando es atribuible a procesos como psoriasis, dermatitis seborreica, dermatitis atópica y otros. Las manifestaciones clínicas de la forma primaria son subjetivas. El escozor, picor, tricodinia y sensaciones disestésicas son el motivo de consulta, muy a menudo coincidiendo con alopecia. Clínicamente la piel del cuero cabelludo puede ser normal o eritematosa. No hay datos de laboratorio o histológicos específicos para un diagnóstico objetivo. Los factores desencadenantes son endógenos como el estrés y alteraciones emocionales y psicopatológicas, o ambientales como los tópicos inadecuados y los cosméticos. El tratamiento debe ser personalizado, incluyendo pimecrólimus, la hidratación con ácido hialurónico, y la mesoterapia con plasma rico en factores de crecimiento (AU)

Effectiveness of Sopoongsan for chronic upper body pruritus in patients with atopic or seborrheic dermatitis: A pilot study protocol for a randomized, double-blind, placebo-controlled, parallel trial.

INTRODUCTION: Chronic pruritus persists for > 6 weeks and is known to decrease patients' quality of life. Due to the complex pathological mechanism of chronic pruritus, there is still a lack of satisfactory therapeutic agents; therefore, complementary therapies are required to improve itching symptoms. In the Republic of Korea, Sopoongsan, an herbal formula, has been used to treat itching, dizziness, and skin paralysis. To our knowledge, this is the first study to evaluate whether Sopoongsan improves chronic pruritus and to identify Sopoongsan-related changes in the immune response in patients with chronic upper body pruritus. METHODS: A randomized, double-blind, placebo-controlled parallel trial will be conducted to assess 20 patients with chronic upper body pruritus for 3 months who have been diagnosed with allergic atopic dermatitis or seborrheic dermatitis. The patients will be randomly allocated to either the placebo-control (n = 10) or treatment (n = 10) group. The total study period will be 8 weeks (i.e., administration of Sopoongsan or placebo drugs for 4 wk and follow-up for 4 wk). Participants will be allowed to receive external treatment, except for antipruritic medications administered orally, throughout the study period. The primary outcome measure will be the numeric rating scale results for itching, whereas the secondary outcome measures will be questionnaire survey (Dermatological Life Quality Index and Epworth Sleepiness Scale) findings and the immune response index, including interferon gamma, interleukin-4, immunoglobulin E, thymic stromal lymphopoietic protein, and histamine, to investigate the biological mechanisms underlying chronic pruritus. DISCUSSION AND CONCLUSIONS: We expect that the results of this study will provide important clinical evidence regarding the effectiveness of Sopoongsan on itching symptoms, quality of life, sleep disturbance, and changes in the immune response. The findings will help elucidate the mechanism underlying the therapeutic effect of Sopoongsan for chronic pruritus and lay the foundation for further studies in this area.

Association between bleeding periodontal pockets and eczemas: Results of the Northern Finland Birth Cohort 1966.

AIM: To investigate whether the periodontal condition as measured by bleeding periodontal pockets is associated with atopic dermatitis, seborrheic dermatitis, and eczema nummulare. MATERIALS AND METHODS: The study population (n = 1871) was obtained from the 46-year follow-up study of the Northern Finland Birth Cohort 1966 study (NFBC1966). The periodontal condition was measured by the number of sites with bleeding periodontal pockets that were ≥4 mm deep. The whole skin of the participants was clinically examined, and diagnoses of skin diseases were made according to the International Classification of Diseases. Prevalence rate ratios (PRR) and 95% confidence intervals (95% CIs) were estimated using Poisson regression models with robust error variance. RESULTS: In this cohort, comprising 46-year-old participants of NFBC1966, the presence of 1-3 and ≥4 bleeding-deepened periodontal pockets (≥4 mm deep) were associated with seborrheic dermatitis (PRR 1.9, 95% CI: 1.3-2.8 and PRR 2.2, 95% CI: 1.4-3.3, respectively) and with eczema nummulare (PRR 1.7, 95% CI: 0.9-3.1 and PRR 1.7, 95% CI: 0.9-3.3, respectively). For non-smokers, the corresponding estimates were 1.7 for seborrheic dermatitis (95% CI: 1.1-2.6) and 1.8 (95% CI: 1.1-3.1) and 1.4 for eczema nummulare (95% CI: 0.7-2.9) and 1.2 (95% CI: 0.5-2.9), respectively. No association was found between bleeding-deepened periodontal pockets and atopic dermatitis. Further adjustments for C-reactive protein, diabetes, and inflammatory diseases did not essentially change the risk estimates among either the total population or the non-smokers. CONCLUSION: Bleeding periodontal pockets appeared to be associated with the presence of seborrheic dermatitis and eczema nummulare.

Seborrheic dermatitis and risk of incident peptic ulcer disease: A nationwide population-based cohort study.

BACKGROUND: Emerging evidence supports a strong association between the skin and the gut. The association between seborrheic dermatitis (SD) and peptic ulcer disease (PUD) was largely unknown. This study aimed to investigate the association of SD and PUD. METHODS: This nationwide population-based cohort study was conducted using the Taiwan's National Health Insurance Research Database. A total of 19 445 participants was recruited. Each patient with a diagnosis of incident SD was matched to four patients without SD using propensity scores based on age, gender, index year, insurance amount, urbanisation level, Charlson comorbidity index (CCI), the presence of comorbidities and medication use. The primary endpoint was the development of incident PUD. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for PUD occurrence in relation to the presence of SD were calculated. RESULTS: Overall, patients with SD had a significantly higher risk for incident PUD than those without SD in both univariable (crude HR = 1.60, 95% CI 1.38-1.86, P < 0.001) and multivariable (adjusted HR = 1.58, 95% CI 1.36-1.83, P < 0.001) Cox proportional hazard regression models. Kaplan-Meier analysis indicated that the cumulative incidence of PUD was consistently higher in individuals with SD than those without SD (log-rank test, P < 0.001). A higher risk of PUD was also found in individuals with SD than those without SD in all stratified analyses by age, gender, CCI and follow-up time. CONCLUSION: Patients with SD may have a higher risk for incident PUD. Further studies are warranted to validate our findings.

Darier Disease Presenting with Recurrent Kaposi Varicelliform Eruption in a 10-year-old Boy with Seborrheic Dermatitis.

We present a case of a 10-year-old boy with a longstanding history of seborrheic dermatitis (SD) referred to the Allergy and Immunology Department for recurrent Kaposi varicelliform eruption (KVE) secondary to herpes simplex 1 (HSV-1) infection and possible primary immunodeficiency. The patient was the second child of non-consanguineous parents, with an older, healthy brother. Family history was negative for primary immunodeficiency and skin disorders. The patient's skin problems began in infancy when he was diagnosed and treated by a dermatologist for SD. From preschool age, he was under the care of a pediatric neurologist and a defectologist for a sensory processing disorder. For the last two years, the patient had been receiving chlorpromazine therapy for aggressive behavior. The first episode of KVE was diagnosed at the age of six, following potent topical corticosteroid therapy for SD and sun exposure, another known risk factor for HSV infection. After the third KVE episode, prophylaxis with oral acyclovir was initiated. The skin changes were treated with topical steroids and oral antibiotics during disease flares, with poor clinical response. On presentation, the patient was in good general health, adipose, and of unremarkable somatic status, except for numerous symmetrical yellowish-brown keratotic papules and plaques on the forehead, cheeks, and the lateral side of the neck (Figure 1). The nail plate had multiple red and white longitudinal streaks and V-shaped notches on the distal free end of the nail plate (Figure 2). The allergy tests revealed increased total immunoglobulin E (IgE) and sensitization to ragweed. Immunological workup showed normal immunoglobulins and good specific immunity (good vaccine response and normal humoral response to HSV-1) but a decreased number of T- cells (CD3+ 1020/µL (1320-3300), CD3+CD8+ 281/µL (390-1100) with normal T-cell response after antigen stimulation. The diagnosis of Darier disease (DD) was confirmed based on medical history, clinical findings and histological finding of focal suprabasal acantholysis and dyskeratosis (Figure 3). Low-dose oral retinoid therapy was initiated with modest clinical response after 6 months of therapy. In the light of recent publication (1), we initiated intravenous immunoglobulin (IVIG) substitution (400 mg/kg every month) with excellent clinical response. After 4 months, the patient's skin improved in terms of reduced inflammation, scab healing, and reduced itching. Acyclovir prophylaxis was continued. The patient had no new episodes of KVE during follow-up. Kaposi's varicelliform eruption (KVE) or eczema herpeticum occurs in a chronic inflammatory skin disease such as atopic dermatitis (AD), SD, Hailey-Hailey disease, allergic contact dermatitis, psoriasis, and DD (2). It is considered a dermatologic emergency due to its high mortality rate if misdiagnosed or left untreated (3). DD is a rare autosomal dominant genodermatosis of variable expressivity caused by mutations in the ATP2A2 gene, which encodes a sarco/endoplasmic reticulum calcium ATPase (SERCA2) highly expressed in keratinocytes (4). The onset of the disease usually occurs between the ages of 6 and 20 years. There are several clinical variants of DD: hypertrophic, verrucous, vesicular-bullous (dyshidrotic), erosive, and predominantly intertriginous forms (4). The fact that skin lesions occurred in infancy and a negative family history for skin diseases could be the reason our patient was initially misdiagnosed with seborrheic dermatitis. Due to the variable expressivity of the disease, it is impossible to exclude the diagnosis in other family members, and genetic testing of the patient and family members is therefore planned. A co-occurrence of neuropsychiatric abnormalities such as epilepsy, mental impairment, and mood disorders have been reported in patients with Darier disease, and these disorders were also present in our patient (5), indicating a correct diagnosis. Patients with DD have a high propensity for severe viral, bacterial, and fungal skin infection, probably due to local disruption of the skin barrier function or as the result of an underlying defect in general host defence (6). The occurrence of KVE in patients with DD is rare (7) and possibly caused by a disturbances in cell-mediated immunity (8). Despite abnormal findings in cellular immunity in some patients with DD, no consistent or specific abnormalities of the immune system have yet been demonstrated (6). Our patient had a decreased number of cytotoxic T-cells with normal T-cell response after antigen stimulation (in contrast with the findings of Jegasothy et al. (6)) and normal humoral response to HSV-1 infection. Recurrent KVE in our patient could be related to immune system dysfunction as an additional risk factor, along with impaired skin barrier. The excellent clinical response to IVIG speaks in favor of the role of antibody immune response in preserving the skin barrier. Occurrence of KVE in patients with mild DD (as in the case of our patient) and in some patients immediately preceding clinical skin manifestations of disease, argues very strongly against the second supposition. The severity of DD is variable and has a chronic course with frequent exacerbations and remissions. Known exacerbating triggers are: heat, sweat, sun exposure, friction, medication, and infection (9,10). The disease is chronic, and management is focused on the improvement of the skin appearance, relief of symptoms (e.g., irritation, pruritus, and malodor), and prevention or treatment of secondary infections. Topical (emollients, corticosteroids, retinoids, 5-fluorouracil, tacrolimus, pimecrolimus), physical (excision, electrodessication, dermabrasion, ablative laser, photodynamic therapy), and systemic (oral antibiotics, antiviral drugs, antimicrobial prophylaxis, vitamin A, retinoids) therapies are among the treatment options, all of which are of limited effect (2,11,12). IVIG substitution could be beneficial in some patients with Darier disease (1). In conclusion, this case highlights the association of DD with impaired cellular immunity and indicates the importance of proper diagnosis due to adequate management and avoidance of possible fatal outcomes. However, whether a subtle abnormality of T-cells in DD predisposes the patient to KVE remains unclear. Possible underlying mechanisms should be investigated further.

A Review of the Current Evidence Connecting Seborrheic Dermatitis and Parkinson's Disease and the Potential Role of Oral Cannabinoids.

Parkinson's disease (PD) is a neurodegenerative disorder associated with multiple comorbidities, including seborrheic dermatitis (SD), which develops in more than half of PD patients. SD in patients with PD can be severe and frequently intractable by traditional topical therapy. Cannabinoids possess anti-inflammatory and neuromodulatory properties working within the intrinsic endocannabinoid system, the activation of which may alleviate the motor symptoms of PD. The effect of cannabinoids on SD is unknown. Here we explore the pathophysiological mechanisms and possible therapeutic role of oral cannabinoids in PD patients with SD, and review speculative mechanisms underlying the association of PD and SD. Current data supporting the use of cannabinoids in both PD and SD, as well as oral cannabinoid safety and tolerability, are presented. Cannabinoids may provide the possibility of simultaneous treatment of both SD and PD. Specific SD studies and additional safety data on oral cannabinoids are needed.

A randomized controlled clinical study of acupuncture therapy for Seborrheic alopecia in young and middle ages: Study protocol clinical trial (SPIRIT compliant).

INTRODUCTION: Seborrheic alopecia (SA) has clinical manifestations, duration of disease, and priorities. In the current situation where there are many and complicated clinical treatments, Western medicine treatment can delay and control the development of the disease and promote hair regeneration. However, some patients may aggravate symptoms after taking the drug, and the condition is easy to repeat after stopping the drug. Acupuncture is an important method for non-surgical treatment of SA, and it has various methods, low side effects, high safety, and simple and economical. Therefore, we will use a clinical randomized controlled study to explore the effect of acupuncture on SA, and provide a new idea and reference for the treatment of this disease. METHODS/DESIGN: We will select 60 patients diagnosed with SA. They will be randomly divided into intervention group and control groups. The control group will be given conventional treatment measures. The intervention group will receive acupuncture. Efficacy will be evaluated by comparing the skin lesion score and dermatological quality of life index before and after treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with SA. TRIAL REGISTRATION NUMBER: CTR2000030430.

Seborrhea herpeticum: cutaneous herpes simplex virus infection within infantile seborrheic dermatitis.

Eczema herpeticum has been well described in the setting of atopic dermatitis (AD) and other dermatoses. We present the case of a 2-month-old infant boy with cutaneous herpes simplex virus (HSV) infection within existing diffuse infantile seborrheic dermatitis. Providers should be aware that cutaneous HSV can be confined to a seborrheic distribution and may represent underlying epidermal dysfunction secondary to seborrheic dermatitis.

Evaluation of dry eye disase and meibomian gland dysfunction with meibography in seborrheic dermatitis.

PURPOSE: To evaluate the dry eye disase and meibomian gland dysfunction with meibography of Seborrheic Dermatit patients. METHODS: A hundred-ten of 50 patients with Seborrheic Dermatitis (group 1) and 100 eyes of 50 healthy individuals (group 2) were enrolled in this prospective study. All subjects were performed a comprehensive ophthalmic examination including lid margin alterations and meibomian gland obstruction assessment, Ocular Surface Disease Index assessment, tear film break-up time test, corneal and conjunctival fluorescein staining assessment, Schirmer test. In addition, upper and lower lids were evaluated for meibomian gland loss with non-contact meibography. The Meibomian glands were graded from grade 0 (no loss of Meibomian glands) to grade 3 (gland loss >2/3 of the total Meibomian glands). RESULTS: The mean ages of Group 1 and Group 2 were 29.1 ± 9.1(range, 18-48) and 30.6 ± 6.3(range, 20-49) years, respectively. MGD(n = 19, %34.5), Meibium gland loss(%36.4 ± 18.1), upper meiboscore (0.7 ± 0.8), lower meiboscore(0.6 ± 0.7) and DED (n = 10, %18.2) were significantly higher in the SD patients compared with the control participants (p = 0.002, p < 0.001, p = 0.011, p = 0.005, p = 0.048, respectively). There was significant relationship between age with Meibomian gland loss, MGD and DED (p = 0.017, p = 0.004, p = 0.002, respectively). CONCLUSIONS: Seborrheic Dermatitis may influence meibomian gland morphology and as a result causing meibomian gland dysfunction and dry eye disase. For this reason, patients with Seborrheic Dermatitis should be evaluated for meibomian gland dysfunction and dry eye disase, and start treatment when needed.

Wound myiasis: the role of entodermoscopy

Abstract: Although wound or traumatic myiasis is common in tropical countries, only recently cases associated with underlying dermatoses, such as seborrheic dermatitis and psoriasis, have been reported. We describe a patient with seborrheic dermatitis and an ulcerated lesion on the scalp, in which the dermatological examination with the aid of dermoscopy allowed the identification of larvae (maggots) compatible with infestation by Cochliomyia hominivorax. Treatment was performed with oral and topical ivermectin, followed by manual extraction of the larvae.

Wound myiasis: the role of entodermoscopy.

Although wound or traumatic myiasis is common in tropical countries, only recently cases associated with underlying dermatoses, such as seborrheic dermatitis and psoriasis, have been reported. We describe a patient with seborrheic dermatitis and an ulcerated lesion on the scalp, in which the dermatological examination with the aid of dermoscopy allowed the identification of larvae (maggots) compatible with infestation by Cochliomyia hominivorax. Treatment was performed with oral and topical ivermectin, followed by manual extraction of the larvae.

Cutaneous manifestations of obesity and themetabolic syndrome.

The cutaneous manifestations of obesity and the associated metabolic syndrome (MetS) may present with a wide variety of cutaneous findings, including acanthosis nigricans, acrochordon, cellulitis, psoriasis, hidradenitis suppurativa, acne, and hirsutism. Being aware of such clinical signs and the underlying systemic disorders may facilitate earlier diagnoses, thereby permitting earlier of therapy initiation and prevention of long-term sequelae. In this process, dermatologists are key figures in the early detection of MetS and its clinical manifestations.

Adult female acne treated with spironolactone: a retrospective data review of 70 cases.

The prevalence of acne in the adult population is increasing, particularly in women. Spironolactone regulates sebaceous gland activity by blocking androgen receptor. To evaluate retrospectively the efficacy of spironolactone in women with acne. Data from 70 women of at least 20 years, treated for their acne between 2010 and 2015 with low-dose spironolactone (≤150 mg/day), were analysed. Remission was defined by the number of retentional lesions inferior or equal to five and inflammatory lesions inferior or equal to two on the face. Variables influencing the response were studied using the Cox model. The mean age was 31.3 years; 39 (56%) women had prior courses of isotretinoin and 53 (76%) had an oral contraception prior to treatment. Remission data from a median treatment period of six months (95% CI: 4-9) were obtained from 47 (71%) women. Markers for a positive response to spironolactone were a high number of inflammatory lesions at inclusion (OR: 1.08; 95% CI: 1.03-1.13; p = 0.001) and relapse with previous isotretinoin (OR: 2.46; 95% CI: 1.09-5.54; p = 0.03). The marker for a negative response was an association with oral contraceptives containing first or second-generation progestin (OR: 2.77; 95% CI: 1.35-5.71; p = 0.005). This retrospective data analysis confirms that the use of low doses of spironolactone is a valuable alternative in women with acne in whom oral isotretinoin has failed. Moreover, the analysis shows that first and second-generation oral contraceptives decrease the efficacy of spironolactone, confirming the interest of using two third or fourth-generation oral contraceptives.