We assessed possible long-term side-effects of isotretinoin therapy in 720 patients who had received one or more courses of treatment, and had a mean follow-up period of 4.9 years (range 2-12 years). Most patients (442) had received a total cumulative dose of 120-200 mg/kg body weight. One hundred and sixty-two patients received a cumulative dose of < 120 mg/kg body weight, and 116 received a cumulative dose > 200 mg/kg. Fifty-two patients (7.2%) reported persistent symptoms during the follow-up period. No correlation was found between age, sex, cumulative dose, or number of courses of isotretinoin and occurrence of reported possible side-effects. The reported symptoms were predominantly musculoskeletal (2%) or mucocutaneous (4.8%), and were mild in all cases. Xeroderma, dry eye syndrome, arthralgia, and possible exacerbation of eczema, were considered to be infrequent but probable long-term side-effects. The findings of this study indicate that isotretinoin in the treatment of acne is a safe drug, with no serious long-term side-effects.
Truncal acne is frequently underdiagnosed despite affecting around half of those with facial acne. The objective was to provide an overview of the literature on the incidence of truncal acne according to age, gender, and acne severity.A narrative review of data from recent large surveys and a literature search in PubMed on the incidence of truncal acne across subgroups of age, gender, and acne severity.The prevalence of truncal acne alone was low, ranging from <1% to 14%, but approximately 30 to 60 percent of individuals with facial acne also had truncal acne depending on the population. In an online survey in the United States of 2,000 respondents aged between 14 -29 years with self-reported active facial and/or truncal acne, the incidence of truncal acne was lower in the 14-20 years subgroup than in the 21-29 years subgroup (49% vs 54%). The incidence of truncal acne was similar in both males and females, while 46 percent of respondents with self-declared clear and mild acne indicated having truncal involvement compared to 60 percent of those with moderate or severe acne.Online surveys have inherent limitations, such as self-reporting and potential confounders.Data suggests that patients with both facial and truncal involvement have earlier onset of acne and more severe acne. Additional adverse psychological impact may arise from having the impression that the disease is spreading and becoming more severe. Raising awareness of truncal acne prevalence and demographics could improve its clinical management to reduce the negative psychological impact.
Background: Acne is a common chronic inflammatory dermatosis of the pilosebaceous unit. It is characterized by seborrhoea, comedone formation and an inflammatory response consistent with defective cellular immunity to Propionibacterium acnes. Objective: The objective of this study was to investigate the immune reactivity of patients with acne compared to healthy controls by examining the response of peripheral blood mononuclear cells (PBMC) to stimulation with P. acnes. Particular focus was placed upon the measuring the production of IL-10 which has established immunoregulatory role. Methods and Patients: Venous blood was collected from 47 acne patients and 40 age and sex matched healthy controls with no prior history of acne. PBMC were cultured and their cytokine response to P. acnes investigated. Results: Pro-inflammatory IL-8 and TNF? secretion from PBMCs was higher in acne patients when stimulated with P. acnes. In contrast, a statistically significant reduction in PBMC secretion of anti-inflammatory IL-10 in acne patients was identified. The impaired production of IL-10 by PBMCs from acne patients was confined to CD14+ cells presumed to be monocytes. The ability of CD14 cells from acne patients to phagocytose P. acnes bacteria was also observed to be defective but the addition of exogenous IL-10 to PBMC cultures restored phagocytic activity. Conclusions: These data suggest that acne patients have a pro-inflammatory cytokine milieu and crucially are unable to contain early inflammatory changes due to a specific defect in immunosurveillance, namely low monocyte IL-10 production. Our observations raise the possibility that acne therapeutics might profitably target IL-10 both as a regulator of pro-inflammatory cytokines and in augmenting the CD14+ cell phagocytic response.
Abstract Background Antibiotics are often combined with other agents to provide topical acne treatments that are effective against both inflammatory and non‐inflammatory lesions and minimize the development of antibiotic resistance. Objectives To compare the clinical effectiveness of two combination treatments for facial acne: a ready mixed, once daily gel containing clindamycin phosphate (1%) plus benzoyl peroxide (5%) (CDP + BPO) and a twice daily solution of erythromycin (4%) plus zinc acetate (1.2%) (ERY + Zn). Methods/patients In this assessor‐blind, randomized study, 73 patients were treated with CDP + BPO once daily and 75 patients with ERY + Zn twice daily. The treatment period was 12 weeks and lesion counts and global improvement were assessed at weeks 1, 2, 4, 8 and 12. Results CDP + BPO showed an earlier onset of action with a faster significant reduction in total lesion counts than ERY + Zn. The proportion of patients with at least a 30% improvement in non‐inflammatory lesions at week 1 was 31.5% for CDP + BPO and 17.3% for ERY + Zn; the corresponding percentages for inflammatory lesions were 39.7% and 29.3%. A difference was also observed at week 2 (53.4% vs. 36.0% for non‐inflammatory lesions and 72.6% vs. 53.3% for inflammatory lesions). The trend in favour of CDP + BPO, although less marked, continued to the end of the study, with reductions in the total lesion count at endpoint of 69.8% for CDP + BPO group and 64.5% for ERY + Zn group. Both treatments were well tolerated. Conclusions CDP + BPO and ERY + Zn are effective treatments for acne but CDP + BPO has an earlier onset of action that should improve patient compliance.
The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes.To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance.The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting "agree" or "strongly agree." All voting was electronic and blinded.The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae.The recommendations are based on expert opinion and made in the absence of high-quality evidence.The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management.
Summary Background In a recent Phase IIa clinical trial, the candidate leishmaniasis vaccine ChAd63-KH was shown to be safe and immunogenic in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). However, its value as a stand-alone therapeutic was unknown. Methods To assess the therapeutic efficacy of ChAd63-KH, we conducted a “window of opportunity” randomized, double-blind, placebo-controlled trial ( Clinicaltrials.gov registration: NCT03969134 ). We aimed to enrol 100 participants (male and female aged 12-50 years) with uncomplicated PKDL of ≥ six months duration. ChAd63-KH (7.5×10 10 viral particles) or saline placebo was administered once intramuscularly. Primary outcomes were safety and efficacy. Safety was determined by adverse event monitoring. Efficacy was the proportion of participants at 90 days post-vaccination with ζ90% improvement in clinical disease. Participants failing to reach this clinical endpoint were offered a standard of care (AmBisome ® ). Secondary outcomes included changes in PKDL severity grade and measurements of vaccine-induced immune response. Findings Between 4 th April 2020 and 17 th June 2022, 86 participants (66 adolescents, 20 adults; 47% female, 53% male) were enrolled and randomised to receive ChAd63-KH or placebo. 75 participants (87%) completed the trial as per protocol. No severe or serious adverse events were observed. At day 90 post vaccination, 6/40 (15%) and 4/35 (11%) participants in the vaccine and placebo groups respectively showed ≥ 90% clinical improvement (RR 1.31 [95% CI, 0.40 to 4.28], p=0.742). There were also no significant differences in PKDL grade between study arms. Whole blood transcriptomic analysis identified transcriptional modules associated with interferon responses and monocyte and dendritic cell activation, confirming vaccine reactogenicity. Interpretation Single dose administration of ChAd63-KH vaccine had no therapeutic efficacy in this subset of Sudanese PKDL patients. Further studies are needed to evaluate whether this vaccine would have therapeutic benefit using alternate dosing regimens or in combination with standard chemotherapy or immune modulation, and whether it has efficacy as a prophylactic vaccine for cutaneous or visceral leishmaniasis. Funding This study was funded by the Wellcome Trust. Research in context Evidence before this study A leishmaniasis vaccine candidate was developed employing chimpanzee adenovirus 63 (ChAd63) to deliver genes encoding two Leishmania antigens, KMP-11 and HASPB1. This vaccine (ChAd63-KH) was previously evaluated for safety and immunogenicity in a Phase I healthy volunteer study and a Phase IIa study in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). It was shown to be safe and immunogenic, warranting further clinical studies to evaluate efficacy as a stand-alone therapeutic in PKDL patients. Added value of this study This clinical trial was designed to evaluate the safety and efficacy of ChAd63-KH in PKDL patients with persistent disease (dermal lesions for ≥ 6 months). If successful, single dose vaccination would significantly improve treatment options currently available to patients. The safety of ChAd63-KH was confirmed, with no severe or serious adverse events observed in trial participants. Approximately 13% of participants had ζ90% improvement in their PKDL over the course of 90 days follow up post vaccination, but this did not differ between vaccine and placebo arms, indicating that this reflected spontaneous cure rather than vaccine efficacy. Immune monitoring using whole blood transcriptomics confirmed the previously reported ability of this vaccine to induce immune responses in humans. Implications of all the available evidence This study indicates that as a stand-alone treatment, single dose vaccination with ChAd63-KH was unable to overcome the immune dysfunction that maintains persistent PKDL. A similar “high bar” has also been encountered in therapeutic vaccine trials for other persistent diseases. Given previous success with other forms of immunochemotherapy in PKDL, future therapeutic vaccine studies in PKDL might also benefit from combining ChAd63-KH vaccination with additional chemotherapy or immune modulation. The prophylactic efficacy of this vaccine against different types of leishmaniasis also remains to be evaluated.
Acne is one of the ten most common diseases worldwide and is the inflammatory skin disease seen most frequently by community physicians and dermatologists. Over the last decade, knowledge of acne pathophysiology and etiologic factors has expanded, resulting in the development of novel treatments that target clinical lesions and improve patient outc
An increased rate of venous ulcer healing with the use of oral enteric‐coated aspirin (300mg) daily has been reported.1 Whether the effect of aspirin in this condition is related to its action on the haemostatic mechanism is unclear, and therefore this study aimed to assess the effect of aspirin on some haemostatic parameters in patients with chronic venous leg ulcers. A double‐blind, randomized, placebo‐controlled, parallel‐group study of haemostatic activity and the effect of aspirin was implemented over a 4‐month period. Twenty patients with venous leg ulcers, and 20 age‐ and sex‐matched controls were studied. Patients received enteric‐coated aspirin (300mg) or placebo (one tablet) daily for 4 months, in addition to standardized local compressive bandaging (Setopress®). Assessments made at recruitment, and at 2 and 4 months, included measurement of total ulcer surface area, haematological and biochemical screening, measurement of coagulation times, coagulation factor VIII:C (FVIII:C) and von Willebrand factor (vWF), and plasminogen activator inhibitor‐1 (PAJ‐1) levels. Procoagulant activity was assessed by a computer‐assisted technique, to determine the rate of thrombin production in vitro. Patients with venous ulcers had increased levels of fibrinogen (P < 0.01), FVIII:C (P < 0.05), vWF (P < 0.05) and PAI‐1 antigen (P < 0.01) compared with controls. Shortening of the coagulation rate, shown by a reduction of the time to generate 50% maxima! thrombin activity in seconds (T5o), was seen in patients, in comparison with control subjects (P < 0.05). T50 was longer in patients receiving aspirin than those receiving placebo, reflecting prolongation of coagulation rate in the aspirin‐treated group. In addition, an increased rate of ulcer healing occurred in subjects receiving aspirin compared with the placebo‐treated group (P < 0.01, P < 0.02 at 2 and 4 months, respectively). No significant change in fibrinogen, FVIII:C, vWF or PAI‐1 levels occurred in either group during the 4‐month period.
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