Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by medications. In addition to tertiary-level supportive care, various systemic therapies have been used including glucocorticoids, intravenous immunoglobulins (IVIGs), cyclosporin, N-acetylcysteine, thalidomide, infliximab, etanercept, and plasmapheresis. There is an unmet need to understand the efficacy of these interventions. OBJECTIVES: To assess the effects of systemic therapies (medicines delivered orally, intramuscularly, or intravenously) for the treatment of SJS, TEN, and SJS/TEN overlap syndrome. SEARCH METHODS: We searched the following databases up to March 2021: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five clinical trial registers, the reference lists of all included studies and of key review articles, and a number of drug manufacturer websites. We searched for errata or retractions of included studies. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) and prospective observational comparative studies of participants of any age with a clinical diagnosis of SJS, TEN, or SJS/TEN overlap syndrome. We included all systemic therapies studied to date and permitted comparisons between each therapy, as well as between therapy and placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as specified by Cochrane. Our primary outcomes were SJS/TEN-specific mortality and adverse effects leading to discontinuation of SJS/TEN therapy. Secondary outcomes included time to complete re-epithelialisation, intensive care unit length of stay, total hospital length of stay, illness sequelae, and other adverse effects attributed to systemic therapy. We rated the certainty of the evidence for each outcome using GRADE. MAIN RESULTS: We included nine studies with a total of 308 participants (131 males and 155 females) from seven countries. We included two studies in the quantitative meta-analysis. We included three RCTs and six prospective, controlled observational studies. Sample sizes ranged from 10 to 91. Most studies did not report study duration or time to follow-up. Two studies reported a mean SCORe of Toxic Epidermal Necrosis (SCORTEN) of 3 and 1.9. Seven studies did not report SCORTEN, although four of these studies reported average or ranges of body surface area (BSA) (means ranging from 44% to 51%). Two studies were set in burns units, two in dermatology wards, one in an intensive care unit, one in a paediatric ward, and three in unspecified inpatient units. Seven studies reported a mean age, which ranged from 29 to 56 years. Two studies included paediatric participants (23 children). We assessed the results from one of three RCTs as low risk of bias in all domains, one as high, and one as some concerns. We judged the results from all six prospective observational comparative studies to be at a high risk of bias. We downgraded the certainty of the evidence because of serious risk of bias concerns and for imprecision due to small numbers of participants. The interventions assessed included systemic corticosteroids, tumour necrosis factor-alpha (TNF-alpha) inhibitors, cyclosporin, thalidomide, N-acetylcysteine, IVIG, and supportive care. No data were available for the main comparisons of interest as specified in the review protocol: etanercept versus cyclosporin, etanercept versus IVIG, IVIG versus supportive care, IVIG versus cyclosporin, and cyclosporin versus corticosteroids. Corticosteroids versus no corticosteroids It is uncertain if there is any difference between corticosteroids (methylprednisolone 4 mg/kg/day for two more days after fever had subsided and no new lesions had developed) and no corticosteroids on disease-specific mortality (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.72 to 9.03; 2 studies; 56 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. IVIG versus no IVIG It is uncertain if there is any difference between IVIG (0.2 to 0.5 g/kg cumulative dose over three days) and no IVIG in risk of disease-specific mortality (RR 0.33, 95% CI 0.04 to 2.91); time to complete re-epithelialisation (mean difference (MD) -2.93 days, 95% CI -4.4 to -1.46); or length of hospital stay (MD -2.00 days, 95% CI -5.81 to 1.81). All results in this comparison were based on one study with 36 participants, and very low-certainty evidence. Adverse effects leading to discontinuation of therapy were not reported. Etanercept (TNF-alpha inhibitor) versus corticosteroids Etanercept (25 mg (50 mg if weight > 65 kg) twice weekly "until skin lesions healed") may reduce disease-specific mortality compared to corticosteroids (intravenous prednisolone 1 to 1.5 mg/kg/day "until skin lesions healed") (RR 0.51, 95% CI 0.16 to 1.63; 1 study; 91 participants; low-certainty evidence); however, the CIs were consistent with possible benefit and possible harm. Serious adverse events, such as sepsis and respiratory failure, were reported in 5 of 48 participants with etanercept and 9 of 43 participants with corticosteroids, but it was not clear if they led to discontinuation of therapy. Time to complete re-epithelialisation and length of hospital stay were not reported. Cyclosporin versus IVIG  It is uncertain if there is any difference between cyclosporin (3 mg/kg/day or intravenous 1 mg/kg/day until complete re-epithelialisation, then tapered off (10 mg/day reduction every 48 hours)) and IVIG (continuous infusion 0.75 g/kg/day for 4 days (total dose 3 g/kg) in participants with normal renal function) in risk of disease-specific mortality (RR 0.13, 95% CI 0.02 to 0.98, 1 study; 22 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. No studies measured intensive care unit length of stay. AUTHORS' CONCLUSIONS: When compared to corticosteroids, etanercept may result in mortality reduction. For the following comparisons, the certainty of the evidence for disease-specific mortality is very low: corticosteroids versus no corticosteroids,  IVIG versus no IVIG and cyclosporin versus IVIG. There is a need for more multicentric studies, focused on the most important clinical comparisons, to provide reliable answers about the best treatments for SJS/TEN.

Contact dermatitis: An important consideration in leg ulcers.

The prevalence of chronic wounds is increasing with the aging population, with 1% to 2% of the worldwide population experiencing leg ulcers and positive patch tests reported in up to 75% of this population. With the introduction of modern dressings and compression therapies, clinicians should be cognizant of the potential risk of contact dermatitis in patients with leg ulcers. Contact dermatitis (both allergic and irritant) to wound products may present as maceration, pain, and overall impaired wound healing. Herein, we review the literature on contact dermatitis to wound-care products.

Concurrent measurement of genital lubrication and blood flow during sexual arousal.

Genital lubrication and blood flow are theoretically related outcomes of women's sexual response that prepare the genitals for sexual activity. Despite its importance for sexual function, few experimental studies have directly assessed genital lubrication or empirically demonstrated how genital lubrication and blood flow relate during sexual arousal. In this study, 36 women viewed stimuli that varied by sexual activity intensity (nonsexual, low-intensity sexual, and high-intensity sexual) while their genital responses were assessed using concurrent measures of genital lubrication (using litmus test strips) and genital blood flow (using laser Doppler imaging). Both measures detected a genital response to high-intensity sexual stimuli relative to nonsexual; however, only the laser Doppler imager was sensitive to varying degrees of genital response elicited by stimuli of different sexual activity intensities. The two measures of genital response were suitable for repeated measurement within a single session. Genital lubrication and blood flow were positively correlated for the high-intensity sexual stimuli. Implications for the assessment of women's genital response and understanding women's sexual arousal are discussed.

A 2017 update: Challenging the cosmetic procedural delay following oral isotretinoin therapy.

For decades it has been widely accepted that elective procedures should be delayed for at least 6-months following completion of isotretinoin therapy. However, numerous 2017 publications demonstrate the need for change in best practice. The evidence has yet to be succinctly summarized in a single article or in a stand-alone quick reference algorithm for physicians. This article's review of all 2017 publications confirms that the 6-month delay is not necessary for all procedures and provides a simple algorithmic approach to summarize the updated recommendations for procedural delay of cosmetic procedures following systemic isotretinoin therapy. This is a useful tool for clinicians and allows patients to receive the most appropriate and timely cosmetic therapy to minimize the psychosocial impact of the skin condition.

Usability, Satisfaction, and Usefulness of an Illustrated Eczema Action Plan.

BACKGROUND: An eczema action plan (EAP) is an individualized tool to help caregivers and patients self-manage eczema. While novel illustrated EAPs have been developed and validated, there is limited literature examining the value of EAPs from patient and caregiver perspectives. OBJECTIVES: The objective of this study was to test the usability, satisfaction, and usefulness of our validated EAP from the perspective of patients and caregivers. METHODS: Consecutive patients from the pediatric dermatology clinic of a tertiary children's hospital from July 2016 to July 2017 were offered enrolment in a prospective survey study; informed consent was obtained from participants. The illustrated EAP was explained to the participant by a trained research assistant. Participants were sent electronic postvisit surveys using Likert scale questions via REDCap on EAP usability and satisfaction (9 items) as well as on usefulness (3 items). RESULTS: Of 233 consecutive clinic patients, 192 participants (82%) were enrolled, and 112 (58%; 85 caregivers and 22 patients) completed the postvisit surveys. Characteristics were similar between responders and nonresponders. Overall, participants rated the usability (96%), satisfaction (85%), and usefulness (78%) of the EAP positively. Education level, experience with eczema, previous dermatology consultation, and participant type (caregiver vs patient) did not significantly affect the usability or usefulness ratings. However, caregivers' overall EAP ratings were significantly higher ( P = .02) than the patients'. CONCLUSION: The caregivers and participants demonstrate that the EAP is a useful and highly usable tool. Future research should examine the effectiveness of EAP use on objective atopic dermatitis outcomes using a pragmatic clinical trial design.

Drug-induced phototoxicity: A systematic review.

BACKGROUND: Phototoxicity has been attributed to numerous oral drugs over the past 60 years. OBJECTIVE: Determine the quality of evidence supporting suspected phototoxicity from oral drugs. METHODS: The MEDLINE and EMBASE databases were searched for all studies that contain original data for drug-induced phototoxicity and were published between May 1959 and December 2016. Study quality was assessed by using a modified Grading of Recommendations, Assessment, Development and Evaluation scale. RESULTS: The review included 240 eligible studies with a total of 2466 subjects. There were 1134 cases of suspected phototoxicity associated with 129 drugs. Most associations were supported by either very low-quality or low-quality evidence (89.1% of the studies). Medications supported by stronger evidence were vemurafenib, nonsteroidal anti-inflammatory drugs, and antibiotics, specifically, fluoroquinolones and tetracyclines. The most frequently reported drugs were vemurafenib, voriconazole, doxycycline, hydrochlorothiazide, amiodarone, and chlorpromazine. Photobiologic evaluation was performed in only 56 studies (23.3%), whereas challenge-rechallenge was done in 10% of cases. LIMITATIONS: Only English-language publications were reviewed. Cases of phototoxicity that had been incorrectly categorized as photoallergy would not have been included. CONCLUSIONS: Most purported associations between oral drugs and phototoxicity are not supported by high-quality evidence. Despite the variable quality of data, clinicians should be aware of the possible consequences of long-term use of culprit drugs.

A unique combination of Rosai-Dorfman disease and mycosis fungoides: a case report.

Rosai-Dorfman disease (RDD) is a rare histiocytic condition of unknown etiology. Patients with RDD classically present with massive painless cervical lymphadenopathy. However, extra-nodal disease occurs in approximately 40% of cases, with the skin being among the most commonly involved sites. Patients with isolated extra-nodal involvement may present without adenopathy. Reports of RDD occurring in patients with Hodgkin's lymphoma, and B-cell lymphoma have been published, but there has only been one previous report of RDD in a patient with a T-cell lymphoma. This case report documents a unique combination of RDD and mycosis fungoides (MF), a cutaneous T cell lymphoma. This report also highlights diagnostic challenges in RDD due to the rarity of the condition and its variable presentation.

Psychological Aspects of Factitious Disorder.

Factitious disorder can present in multiple health care settings, with patients intentionally producing symptoms to assume the sick role. This assumption of the sick role can result in multiple hospitalizations with unnecessary diagnostic workup, as well as invasive diagnostic procedures that can lead to worrisome side effects. Differential diagnoses that should be ruled out include malingering, somatic symptom disorder, and anxiety disorders. For many providers, patients with factitious disorder can be a challenge to treat because the etiology of the disorder remains unclear. There are multiple psychological theories that attempt to explain the motivation and thought process behind the voluntary production of symptoms. Some of these theories have addressed disruptive attachments during childhood, possible intergenerational transfer of the disorder, personal identity conflicts, somatic illness as a form of masochistic activity toward oneself, and intrapsychic conflicts. Confrontation and psychotherapy with a multidisciplinary team has been proposed as a form of treatment. An understanding of the psychological factors associated with factitious disorder can help providers understand the rationale behind the patient's presentation and aid in the formulation of a treatment plan.

A Systematic Review on Oral Isotretinoin Therapy and Clinically Observable Wound Healing in Acne Patients.

The association between isotretinoin and atypical wound healing remains controversial. It is common practice to delay elective procedures for 6 to 24 months after oral isotretinoin therapy. The studies supporting common practices (SCP) recommend extending this period to include the 6 to 24 months preceding treatment. The opposing studies (challenging common practices; CCP) state that the rate of scarring in isotretinoin patients is low and that delaying elective procedures is unnecessary. These practices impact a large number of dermatology patients undergoing acne treatment. This systematic review compiled articles obtained from online databases and examined data from both SCP and CCP studies. The inconsistencies in the reported data and the methodological flaws in the literature preclude any firm conclusions that can resolve the controversy. As such, this review demonstrates that there is insufficient evidence to either corroborate or refute delaying elective procedures in isotretinoin acne patients. Although the recent literature trends toward removing the procedural delay, we advocate for clinicians to consider the research presented in this review in the context of their own clinical experience and each individual patient's situation. The possible negative procedural outcomes must be weighed against the severity of the patient's acne scarring and the psychosocial impact of this scarring on the patient.

Hair pull test: Evidence-based update and revision of guidelines.

BACKGROUND: The hair pull test lacks validation and has unclear pretest guidelines. OBJECTIVE: We sought to quantify normal hair pull test values and elucidate the effect of pretest hair washing and brushing. The impact of hair texture and lifestyle was also examined. METHODS: Participants (n = 181) completed a questionnaire recording demographics, medications, and hair health/history. A single hair pull test (scalp vertex) was performed. RESULTS: The mean number of hairs removed per pull was 0.44 (SD 0.75). There was no significant difference in the mean number of hairs removed regardless of when participants washed (P = .20) or brushed (P = .25) their hair. Hair pull test values were similar between Caucasian-, Asian-, and Afro-textured hair. There was no significant difference in hair pull values between participants taking medications affecting hair loss and participants not taking these medications (P = .33). Tight hairstyles did not influence hair pull test values. LIMITATIONS: Participant hair washing and brushing could not be controlled during the study, but this information was documented and analyzed. CONCLUSION: Normal values for the hair pull test should be reduced to 2 hairs or fewer (97.2% of participants). The current 5-day restriction on pretest hair washing can be reduced and brushing be made permissible.

The Clitoral Photoplethysmograph: A Pilot Study Examining Discriminant and Convergent Validity.

INTRODUCTION: The clitoral photoplethysmograph (CPP) is a relatively new device used to measure changes in clitoral blood volume (CBV); however, its construct validity has not yet been evaluated. AIM: To evaluate the discriminant and convergent validity of the CPP. For discriminant validity, CBV responses should differ between sexual and nonsexual emotional films if the CPP accurately assesses clitoral vasocongestion associated with sexual arousal; for convergent validity, CBV responses should significantly correlate with subjective reports of sexual arousal. METHODS: Twenty women (M age = 21.2 years, SD = 3.4) watched neutral, anxiety-inducing, exhilarating, and sexual (female-male sex) audiovisual stimuli while their genital responses were measured simultaneously using vaginal and clitoral photoplethysmographs and CPPs. Most of these participants continuously reported sexual arousal throughout each stimulus (n = 16), and all reported their sexual and nonsexual affect before and after each stimulus; subjective responses were recorded via button presses using a keypad. MAIN OUTCOME MEASURES: Vaginal pulse amplitude (VPA), CBV, and self-reported sexual arousal and nonsexual affect were used as main outcome measures. RESULTS: CBV demonstrated both discriminant and convergent validity. CBV responses were similar to VPA responses and self-reported sexual arousal; all responses differed significantly as a function of stimulus content, with the sexual stimulus eliciting greater relative changes than nonsexual stimuli. CBV, but not VPA, was significantly (negatively) correlated with continuous self-reported sexual arousal during the shorter sexual stimulus. CBV was significantly negatively correlated with VPA for the shorter sexual stimulus. CONCLUSION: CBV may be a valid measure of women's genital sexual arousal that provides complementary information to VPA and correlates with self-reported sexual arousal. Given our relatively small sample size, and that this is among the first research to use the CPP, the current findings must be replicated. More research using the CPP and other devices is required for a more comprehensive description of women's physiological sexual arousal.