Thyroid Storm in Lupus: A Rare Cause of Unrelenting Pyrexia.

Systemic lupus erythematosus may present with fever, and it is a challenge to attribute fever to a particular cause. Very rarely it can be due to hyperthyroidism. Thyroid storm is a medical emergency causing unrelenting pyrexia. Here we report a case of a young female who first presented as fever of unknown origin (FUO), was subsequently diagnosed as neuropsychiatric lupus, and in whom the cause of unrelenting high fever, which did not respond to adequate immunosuppression to quell disease activity, was documented to be thyroid storm after excluding all other causes such as infection and malignancy. To our knowledge, this is the first case of this kind reported in literature, although cases of thyrotoxicosis preceding or following the diagnosis of lupus is known. Her fever resolved after starting antithyroid drugs and beta blockers.

A Rare Case of Unilateral Xanthogranulomatous Ureteritis Mimicking an Inferior Vena Cava Tumor.

Xanthogranulomatous pyelonephritis (XPG) is a known clinical entity; however, the further progression of this inflammatory pathology to adjacent organs, including the ureter, bladder and urethra, is extremely rare. Xanthogranulomatous inflammation of the ureter is a chronic inflammatory state where foamy macrophages are seen in the lamina propria along with multinucleated giant cells and lymphocytes forming a granulomatous inflammation, which is benign. Based on its appearance on computed tomography (CT) scan images, it can easily be misidentified as a malignant mass, and the patient can be subjected to surgery that can lead to complications. Here we present a case of an elderly male with a known case of chronic kidney disease with uncontrolled type 2 diabetes mellitus who presented with fever and dysuria. Upon further radiological investigations, the patient had underlying sepsis and was seen to have a mass involving the right ureter and inferior vena cava. Upon biopsy and histopathology, he was diagnosed with xanthogranulomatous ureteritis (XGU). The patient underwent further treatment and was followed up.

Post-COVID Multisystem Inflammatory Syndrome-Adult Leading to Cardiomyopathy and Autoimmune Thyroiditis: A Case Report.

The Coronavirus disease pandemic is an evolving disease with myriad presentations and sequelae. Multisystem inflammatory syndrome in adults (MIS-A) can affect various organ systems, including cardiovascular, gastrointestinal, and neurologic systems, with fever and abnormally increased inflammatory markers without significant respiratory affection. This is a well-known complication in children (MIS-C). Validated clinical criteria are used to diagnose this condition. Long-term sequelae of MIS-A are unclear and underreported. Here, we describe a case of Post-COVID-19 MIS-A who presented with cardiac dysfunction, hepatitis, and acute kidney injury and recovered well with steroids. He was left with persistent cardiomyopathy and thyroiditis with hypothyroidism which to date has not fully recovered. This case emphasizes that the sequelae of COVID-19 and its pathophysiology are not fully understood, and more research is needed to predict and prevent the same.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

Platelet derived exosomes disrupt endothelial cell monolayer integrity and enhance vascular inflammation in dengue patients.

Background: Thrombocytopenia is the most notable phenomenon in dengue. Activation status of platelets and interaction of platelets with endothelium contribute towards dengue disease pathogenesis. Platelets are the major cell types known to release extracellular vesicles, especially exosomes in circulation. However, the role of platelet derived exosomes (PLT-EXOs) in endothelial dysfunction during dengue infection remains unknown. Methods: In this study, we recruited 28 healthy subjects and 69 dengue patients categorized as WS- (n=31), WS+ (n=29) and SD (n=9). Platelets were isolated from platelet rich plasma of dengue patients and their activation was assessed by flow cytometry. PLT-EXOs were isolated by ultracentrifugation method. Western blot analyses were performed to characterize the exosomes. Exosome uptake experiment was carried out to see the internalization of exosomes inside endothelial cells (HUVECs). To observe the effect of exosomes on endothelial cells, exosomes were added on HUVECs and expression of adherens and tight junctional proteins were examined by immunofluorescence assay and western blot. Expression levels of vascular injury markers were measured in the culture supernatants of Exosome-HUVEC coculture and sera of dengue patients by MSD-multiplex assay. Results: As compared to healthy subjects, CD41/CD61 expression was significantly reduced (p<0.0001) and CD62p expression was significantly increased (p<0.0001) on platelets in dengue patients. PLT-EXOs isolated from the dengue patients showed higher expression of CD63 and CD9 proteins than the healthy subjects. With in-vitro immunofluorescence assays, we illustrated the internalization of PLT-EXOs by the HUVECs and observed disruption of endothelial cell monolayer integrity in the presence of PLT-EXOs from WS+ and SD patients. Furthermore, the significant reduction in the expressions of ZO-2, VE-Cadherin and CD31 in endothelial cells following exposure to PLT-EXOs from the dengue patients provide direct evidence of PLT-EXOs mediated vascular permeability. PLT-EXOs stimulated the release of inflammatory markers CRP, SAA, sVCAM-1 and sICAM-1 in the supernatants of HUVEC cells. Importantly, significantly higher levels of CRP, sVCAM-1 and sICAM-1 in the sera of severe than mild dengue patients (p<0.0001) suggest their role in disease severity. Conclusions: In summary, our data suggest that PLT-EXOs promote vascular leakage via release of proinflammatory mediators and compromise vascular barrier integrity in dengue patients.

A masquerade: An uncommon presentation of a dual infection of leprosy and human immunodeficiency virus.

Leprosy and human immunodeficiency virus (HIV) often mimic clinical features of connective tissue disease (CTD). They can present such as lupus, rheumatoid arthritis, scleroderma, or overlap syndromes and it sometimes creates confusion about the diagnosis. Serology may not be enough to differentiate the two and effective tissue biopsies are often the answer. We report the case of a 38-year-old female, who presented clinically with features of multisystem involvement suspected to be CTD, but was found to have dual infection: HIV and borderline tuberculoid leprosy.

A study of non-alcoholic fatty liver disease-liver fat score in overweight and obese individuals.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the commonest liver pathologies and is increasing due to increasing obesity. Non-alcoholic fatty liver disease-liver fat score is a non-invasive diagnostic tool with a sensitivity and specificity of 95%. Methods: This was a cross-sectional observational study on 50 overweight and obese individuals with a body mass index (BMI) of more than or equal to 25 kg/m2 and fatty liver on ultrasonography (USG). Alcoholics (≥30 g/day for men and ≥20 g/day for women), other etiologies like drugs and patients who had bowel resection surgeries for obesity were excluded from the study. Non-alcoholic fatty liver disease-liver fat score of more than -0.64 ruled in NAFLD. Data were entered into Microsoft Excel and analyzed using the SPSS (Statistical Package for Social Sciences) Software 20. Results: About 33/50 patients had a score of more than -0.64. Metabolic syndrome was present in 29 (58%), dyslipidemia in 38 (76%), and diabetes mellitus (46%) was the commonest comorbidity. There was a statistically significant difference in the mean age, weight, BMI, blood pressure, liver enzymes, fasting lipid profile, serum albumin, glycosylated Hemoglobin A1C (HBA1C), international normalised ratio (INR), and fasting blood sugars between the two groups with scores >-0.64 and ≤-0.64. There was a negative correlation of high-density lipoprotein and a positive correlation of liver enzymes, triglycerides, low-density lipoprotein, total cholesterol, fasting blood sugar level, and HBA1c with a score of >-0.64. Conclusion: Higher BMI, metabolic syndrome, diabetes mellitus, and dyslipidemia were significantly associated with a score of >-0.64. This score confirmed the ultrasonographically diagnosed fatty liver.

A study of clinical, radiological features and HLA-B27 serology of axial spondyloarthropathy with comparison of radiographic and non-radiographic disease.

Background: Axial spondyloarthropathy is a type of disease which affects the axial skeleton affecting productive years. Methods: This was a cross-sectional, observational study in which 28 consecutive patients more than 16 years of age, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial spondyloarthropathy were included. They were further sub-grouped into radiographic and non-radiographic axial spondyloarthropathy. Clinical features, joint involvement, measurements, HLA-B27 serology, and disease activity were evaluated. Data was entered into Microsoft Excel, and SPSS (Statistical Package for Social Sciences) software 2.0 was used for analyzing the data. Results: Mean age was 28.5 ± 6.3 years. 85.7% were males. Inflammatory low back pain was the most common clinical feature at presentation (89.2%). Enthesitis was the most common extra-articular feature seen in 35.7% of patients. 42.8% were non-radiographic axial spondyloarthritis. 85.7% of patients were HLA-B27 positive. 50% of patients had bone marrow edema on MRI, and only one patient had ankylosis indicating predominantly early disease. 50%-70% of our patients had high disease activity and 89.3% were responding well to non-steroidal anti-inflammatory drugs (NSAIDs). There was no significant difference between the radiographic axial spondyloarthritis group and the non-radiographic group except for elevated C-reactive protein (CRP). Conclusion: Ankylosing spondylitis in western India occurs mostly in the age group of 20-30 years, suggesting affection of productive age group. There was a delay of diagnosis for approximately three years from the onset of symptoms. There was a positive association with HLA-B27 in majority of the patients. Most of our patients had early disease based on radiological findings, suggesting that there was room for therapeutic intervention before irreversible ankylosis had set in.

Efficacy and tolerability of three topical acne treatments by body mass index: post hoc analysis including overweight and obese patients.

BACKGROUND: Acne prevalence may be higher in overweight/obese individuals, potentially due to hormonal, inflammatory, and/or dietary factors. However, the effects of body mass index (BMI) on topical acne treatments are largely unknown. METHODS: Post hoc analyses of changes in inflammatory/noninflammatory lesions and treatment success were conducted using phase 3 data: clindamycin phosphate/benzoyl peroxide (CP/BPO) 1.2%/3.75% gel (NCT01701024); tretinoin 0.05% lotion (NCT02965456 and NCT02932306; pooled); and tazarotene 0.045% lotion (NCT03168321 and NCT03168334; pooled). Data were analyzed by BMI subgroups: <25kg/m2 (underweight-to-normal), 25-<30kg/m2 (overweight), and ≥30kg/m2 (obese). RESULTS: Among participants analyzed (CP/BPO = 495; tretinoin = 1,636; tazarotene = 1,612), ∼20-25% were overweight and 15-20% were obese. At week 12, mean percent changes from baseline in inflammatory lesions were: CP/BPO (overweight: -63.2%, obese: -56.0%); tretinoin (-57.6%, -53.1%); tazarotene (-59.9%, -56.8%). Mean changes in noninflammatory lesions were: CP/BPO (-54.2%, -50.8%); tretinoin (-51.6%, -44.9%); tazarotene (-56.7%, -54.6%). Treatment success rates with active treatment ranged from 16.2% to 33.5% across BMI groups. CONCLUSIONS: CP/BPO 1.2%/3.75% gel, tretinoin 0.05% lotion, and tazarotene 0.045% lotion were all effective in reducing acne lesions by ≥45% in overweight/obese patients with moderate-to-severe acne, comparable to the underweight-to-normal group. Efficacy of these topical acne treatments is not greatly impacted by BMI and may be affected more by the formulation.

A Study of Haematological Profile in Newly Diagnosed Rheumatoid Arthritis and its Correlation with Disease Activity.

Rheumatoid Arthritis is a chronic inflammatory disease of unknown etiology characterised by presence of symmetric involvement of multiple joints, mainly small joints that rapidly progresses to multisystem inflammation. Common haematological abnormalities observed are anemia,leucocytosis, neutropenia, thrombocytosis, thrombocytopenia, eosinophilia and haematological malignancies. This study is aimed at the various haematological parameters observed in newly diagnosed patients of rheumatoid arthritis and correlating it with disease activity measured by indices like DAS 28 CRP and HAQDI. MATERIAL: Patients more than 16 years of age and newly diagnosed cases of rheumatoid arthritis according to the ACR EULAR 2010 criteria who presented in the rheumatology opd were included in the study. A total of 20 patients fulfilling the inclusion criteria were studied.Any patient with active blood loss from any site, infection,chronic liver or kidney disease, malignancies,hematological diseases,those already on disease modifying drugs,other autoimuune diseases were excluded from the study. OBSERVATION: Out of 20 patients of rheumatoid arthritis studied,55%(11) had anemia of chronic disease and 27.5%(5) had iron deficiency anemia,3%(1) had eosinophilia. The disease activity was measured using DAS 28 CRP and HAQ DI. A negative correlation was observed between Hb level and disease activity whereas a positive correlation was observed between platelet count and disease activity. CONCLUSION: In our study it was observed that Hb is significantly lower in patients with high disease activity whereas platelet count and MPV are significantly higher with high disease activity compared to patients with low to moderate disease activity.So, from Hb level, platelet count and MPV, we can predict disease activity in RA patients which can guide us for proper and aggressive management to prevent further disease progression.

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

Assessment of Depression, Anxiety, Stress, and quality of life in rheumatoid arthritis patients and comparison with healthy individuals.

BACKGROUND: Rheumatoid arthritis (RA) is a disabling condition that results in considerable suffering and negatively impacts an individual's psychological, financial, social, and quality of life (QoL). Pain, fatigue, and disabilities, which may be considered as stress factors, are common challenges that may subsequently lead to psychological distress. AIM: Assessment of Depression, Anxiety, Stress, and QoL in RA patients and Comparison with healthy individuals. MATERIALS AND METHODS: This cross-sectional analytical study included 50 RA patients who have reported to a tertiary health care center on outpatient basis and an equal number of age- and sex-matched healthy individuals. The study was conducted after obtaining Institutional Ethics Committee approval and informed consent of the participants. Patients were assessed based on Disease Activity Score incorporating erythrocyte sedimentation rates, Depression Anxiety Stress Scale (DAS21), Health Assessment questionnaire, Visual Analog Scale, and Multidimensional scale of Perceived Social Support. RESULTS: Levels of anxiety, depression, and stress in patients with RA were significantly higher as compared to age- and sex-matched healthy controls. RA patients had significantly lower scores on total social support, as well as social support of family and friends. However, there was no difference between RA patients and healthy controls on social support from significant others. CONCLUSION: Patients with RA had significantly higher levels of anxiety, depression, and stress and significantly lower levels of social support compared to age- and sex-matched healthy controls. The therapeutic implications of these findings need further evaluation.

The Effects of Once-Daily Tretinoin 0.05% Lotion on Quality of Life in Patients with Moderate-to-Severe Acne Vulgaris.

BACKGROUND: In two phase III clinical trials of patients with moderate-to-severe acne (NCT02932306, NCT02965456), tretinoin 0.05% lotion reduced inflammatory and noninflammatory lesions relative to vehicle lotion, with low potential for cutaneous irritation. OBJECTIVE: Data from these studies were analyzed post hoc to investigate the effects of tretinoin 0.05% lotion on patient-reported quality of life, as assessed using the Acne-Specific Quality of Life Questionnaire (Acne-QoL). METHODS: Mean changes from baseline to week 12 in Acne-QoL scores were analyzed in the pooled intent-to-treat population and a subgroup with treatment success (≥ 2-grade improvement on the Evaluator's Global Severity Scale and rating of "clear" or "almost clear"). Pearson correlations were conducted in the pooled intent-to-treat population to assess the relationship between the Acne-QoL acne symptoms domain and each of the other three domains. RESULTS: In the pooled intent-to-treat population (n = 1640), greater mean improvements were found with tretinoin 0.05% lotion vs vehicle in all four domains: self-perception (mean change: 7.4 vs 6.7); role-emotional (6.8 vs 6.0); role-social (4.8 vs 4.6); acne symptoms (6.5 vs 5.6); all p < 0.05. Relative to the intent-to-treat population, participants who experienced treatment success with tretinoin 0.05% lotion had higher (better) mean Acne-QoL scores at week 12. Correlations between acne symptoms and the other three domains were found at baseline and week 12 (p < 0.05). CONCLUSIONS: Participants with moderate-to-severe acne reported better quality of life after 12 weeks of treatment with tretinoin 0.05% lotion. Clinical improvements in acne symptoms may have contributed to these outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02932306, NCT02965456.

A Split-face, Controlled Study to Assess the Compatibility of Tretinoin 0.05% Acne Lotion with Facial Foundation Makeup.

OBJECTIVE: This study was conducted to assess compatibility of tretinoin 0.05% acne lotion with foundation makeup. DESIGN: This was a single-center, evaluator-blinded, randomized, controlled clinical trial. Participants were randomized to apply tretinoin 0.05% lotion to either the right or left side of the face before applying full-face foundation makeup. SETTING: Participants were enrolled at a single center in the United States. PARTICIPANTS: Female individuals aged 18 to 50 years who used facial foundation makeup ≥5 days per week were included. MEASUREMENTS: Investigator-assessed grading for foundation coverage and participant evaluations of makeup appearance were conducted at post-makeup application (Post-Makeup) and Hour 6 (6H) timepoints. Antera 3D® images were taken for skin texture roughness analysis and tolerability evaluations were performed at baseline, post-tretinoin application, Post-Makeup, and 6H timepoints. RESULTS: A total of 30 participants were enrolled and 29 completed the study. There were no significant differences between tretinoin treated and untreated sides for any outcomes of investigator-assessed grading of foundation (percentage coverage, blotchiness, overall coverage, skin tone evenness, visual smoothness). There was a small but statistically significant worsening in percent coverage at 6H versus Post-Makeup on the untreated side, but not the treated side. As rated by participants, even/full coverage and skin smoothness were significantly better on the tretinoin-lotion treated versus the untreated side. Three-dimensional imaging showed there were no significant differences in skin roughness between the treated and untreated sides. Participants reported overall satisfaction with the tretinoin lotion-treated side. CONCLUSION: Tretinoin 0.05% lotion did not interfere with facial makeup application or wearability and was well tolerated.

Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris: assessment of safety and tolerability in subgroups.

Background: Topical tretinoin's role in acne has been established through evidence-based guidelines. Cutaneous irritation and potential to cause or exacerbate postinflammatory hyperpigmentation (PIH) may limit use.Objective: Evaluate safety and tolerability of novel polymeric formulation of tretinoin 0.05% lotion in moderate-to-severe acne.Methods: One thousand six hundred and forty patients randomized to tretinoin 0.05% lotion or vehicle in two double-blind placebo-controlled 12-week studies. Investigator-evaluated cutaneous safety (erythema and scaling) and patient-reported tolerability (itching, burning/stinging) assessed using a scale of 0 (none) to 3 (severe). Hyper- and hypo-pigmentation evaluated at each study visit. A number of subpopulations were investigated.Results: Tretinoin 0.05% lotion was considered safe and very well tolerated. Only application site pain (3.1%), dryness (3.7%) and erythema (1.4%) were reported by >1% or patients. Treatment-related adverse events were particularly rare (≤2%) in Hispanic and male subpopulations, and lower in adult females. The severity of cutaneous safety and tolerability scores remained <0.5 (where 1 = mild) and were generally lower than baseline severity. Tretinoin 0.05% lotion did not appear to cause or exacerbate PIH.Conclusions: A novel polymeric formulation of tretinoin 0.05% lotion provides a highly favorable safety and tolerability profile, with an incidence of erythema, dryness, and skin burning lower than that previously reported with other formulations of tretinoin.

Novel Tretinoin 0.05% Lotion for the Once-daily Treatment of Moderate-to-Severe Acne Vulgaris in an Adult and Adolescent Female Population

Background: Acne vulgaris (acne) is a common dermatological condition typically associated with adolescents, affecting about 85% of young people. However, it is also prevalent and persistent into adulthood, particularly in females. The efficacy of tretinoin in acne is well documented with large pivotal studies. The first lotion formulation of tretinoin was developed to provide an important alternative option to treat acne patients who may be sensitive to the irritant effects of other tretinoin formulations. Objective: To determine whether efficacy and safety of tretinoin 0.05% lotion was similar in adolescent (<18 years) and adult (>=18 years) women with moderate-to-severe acne. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe acne. Female subjects (aged 9 to 58 years, N=909) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout. Results: At week 12, mean percent reduction in inflammatory and noninflammatory lesion counts in female subjects were 56.9% and 51.7%, respectively, compared with 47.1% and 34.9% with vehicle (P=<0.001). Similar results were seen in adult and adolescent females in terms of reduction in inflammatory lesion counts with tretinoin 0.05% lotion; reduction in noninflammatory lesions was significantly greater in adult females (P=0.002). Treatment success was achieved by 23.6% of female subjects by week 12, compared with 13.5% on vehicle (P<0.001). Although treatment success was somewhat greater in adult females (24.6% versus 21.6%), the difference was not significant. The majority of AEs were mild and transient. There were five serious AEs (SAEs) reported (4/1, adult/adolescent, respectively). The most frequently reported treatment related AEs with tretinoin 0.05% lotion were application site pain (3.0%/5.7%), and application site dryness (4.9%/6.4%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Slight increases in mean scores were observed for scaling, burning and stinging within the first four weeks and appeared to be transient. Conclusions: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in female acne. Noninflammatory lesion count reduction was significantly greater in adult females compared with adolescent females. The new lotion formulation was well-tolerated. J Drugs Dermatol. 2019;18(2):178-188.

Novel Tretinoin 0.05% Lotion for Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris in a Hispanic Population

Background: Acne vulgaris (acne) is the most common dermatologic disease seen in a racially, geographically, politically, culturally, and socioeconomically diverse Hispanic population. Despite their growing demographics in the US, there are few studies evaluating acne treatment in this population. Potential for skin irritation and dryness, as well as pigmentary changes are key concerns. The first lotion formulation of tretinoin was developed using novel polymerized emulsion technology to provide an important alternative option to treat these acne patients who may be sensitive to the irritant effects of other tretinoin formulations. Objective: To determine the efficacy and safety of tretinoin 0.05% lotion in treating moderate-to-severe acne in a Hispanic population. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe acne. Hispanic subjects (aged 11 to 50 years, N=766) were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout using a 4-point scale where 0=none and 3=severe. Results: At week 12, mean percent reduction in inflammatory and noninflammatory lesion counts were 60.1% and 53.0%, respectively, compared with 51.1% and 38.7% with vehicle (P≤0.001) in the Hispanic population. Treatment success was achieved by 19.6% of subjects by week 12, compared with 12.7% on vehicle (P=0.015). The majority of AEs were mild and transient. There were four serious AEs (SAEs) reported (two each group) unrelated to treatment. Incidence of treatment-related AEs with tretinoin 0.05% lotion was lower than in the overall study population; the most frequently were application site pain (2.0%), dryness (1.4%), and erythema (1.2%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate at baseline and improved by week 12. There were slight transient increases in scaling and burning over the first four weeks. Hyperpigmentation severity reduced progressively with treatment. Conclusions: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory acne lesions in a Hispanic population. The new lotion formulation was well-tolerated, and all treatment-related AEs were both mild and transient in nature. J Drugs Dermatol. 2019;18(1):32-38.

Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in a preadolescent population.

BACKGROUND: Acne vulgaris (acne) is a common skin condition in children and adolescents. Efficacy of tretinoin is well documented in studies that included pediatric patients (12-18 years of age). With acne routinely presenting in younger patients, data are needed in this important group. Lotion formulations are commonly used across dermatology and are well liked by patients. OBJECTIVE: To evaluate the safety and efficacy of a novel once-daily tretinoin 0.05% lotion in preadolescent subjects (≤ 13 years) with moderate-to-severe acne. METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate-to-severe acne. Preadolescent subjects (N = 154) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory/noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability evaluated throughout. RESULTS: At Week 12, mean percent reduction in inflammatory and noninflammatory lesion counts were 49.5% and 44.0% compared with 31.4% and 18.8% with vehicle (both P = 0.001). Treatment success was achieved by 23.7% of subjects by Week 12, compared with 7.2% (P = 0.009). The majority of AEs were mild and transient: most frequently were application site pain (5.6%) and application site dryness (2.8%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by Week 12. CONCLUSIONS: Tretinoin 0.05% lotion was significantly more effective than vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in preadolescent acne. It was well tolerated, with all treatment-related AEs deemed mild or moderate.

Novel Tretinoin 0.05% Lotion for the Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris: Assessment of Efficacy and Safety in Patients Aged 9 Years and Older.

BACKGROUND: Topical tretinoin has been extensively studied in clinical trials, and its essential role in the treatment of acne vulgaris (acne) established through evidence-based guidelines. OBJECTIVE: To evaluate efficacy, safety, and tolerability of a novel tretinoin 0.05% lotion in moderate-to-severe acne in patients aged 9 years and older. METHODS: A total of 1640 patients, 9-58 years of age were randomized to receive tretinoin 0.05% lotion or vehicle in two double-blind, placebo-controlled 12-week, 2-arm, parallel group studies evaluating safety and efficacy (inflammatory and noninflammatory lesion counts and acne severity using Evaluator Global Severity Scores [EGSS]). In addition, patients completed a patient satisfaction survey (PSS), Acne-specific quality of life (QoL) questionnaire and assessed their facial skin for shininess/oiliness improvement. The data from these two independent studies were pooled and analyzed. RESULTS: Tretinoin 0.05% lotion demonstrated statistically significant superiority to vehicle in reducing inflammatory and noninflammatory lesion counts (both P less than .001) at week 12 and improving acne severity (P less than .001). At week 12, mean percent change in inflammatory and noninflammatory lesions were 52% and 46%, respectively. Treatment success (a 2-grade improvement in EGSS and 'clear' or 'almost clear' was reported in 18% of patients. Tretinoin 0.05% lotion also showed significantly greater benefits relative to vehicle control in terms of patient satisfaction (P less than .001) and acne-specific QoL domains. Tretinoin 0.05% lotion was very well tolerated with no substantive differences in cutaneous tolerability among treatment groups. No patients discontinued treatment because of adverse events. LIMITATIONS: Data from controlled studies may differ from clinical practice. CONCLUSIONS: Tretinoin 0.05% lotion provides statistically significant greater efficacy than vehicle with a highly favorable safety and tolerability profile in moderate-to-severe acne patients. J Drugs Dermatol. 2018;17(10):1084-1091.