Oral Tetracycline Research Articles

Comparison of Efficacy And Safety of Isotretinoin Versus Lymecycline Capsule For The Treatment of Acne Vulgaris

Background: Acne vulgaris is a very common condition which can cause significant physical and psychological morbidity. Oral retinoids and tetracyclines have a major role in acne treatment. Isotretinoin (13-cis-retinoic acid) is the only therapy that impacts on all of the major aetiological factors implicated in acne. Another agent is lymecycline, a tetracycline antibiotic have an antibacterial action against P. acnes and also an anti-inflammatory action and used for treatment of acne. Objectives: To determine the efficacy and safety of Isotretinoin capsules versus Lymecycline capsule in treatment of mild to moderate facial acne vulgaris. Materials & method: This open labelled, randomized study was conducted in Department of Dermatology and Venereology, Dr. Sirajul Islam Medical College & Hospital Ltd., Dhaka, from December 2021 to May 2022. Patients of mild to moderate facial acne vulgaris were enrolled for study. Clinical examination and relevant investigation were done meticulously. A total number of 50 patients was selected and randomization was done 1:1 parallel design into two groups (group-A and group-B), each of which included 25 patients. Group A patients received Isotretinoin and group B patients were given Lymecycline. Patients were followed up on 2nd, 4th, 8th and finally on 12th week to see clinical improvement and adverse effects. All information was recorded in data collection sheet. Result: The mean age was found 20.4±5.7 years in group A and 19.9±6.9 years in group B. The mean age difference was not statistically significant (p>0.05) between two groups. Male to female ratio was almost 1:3 in the whole study patients. Mean score for open comedone (0.28±0.22 vs. 2.2±1.13), closed comedone (1.92±0.19 vs. 2.08±0.25), papule (0.82±0.29 vs. 1.27±1.04) and pustule (0.85±0.33 vs. 1.19±0.39) was identical in group-A and B respectively and significantly better reduction of acne score (p=0.001) in the group A than the group B. It was evident that abdominal discomfort (4.0% vs. 32.0% in group A & B), diarrhea (0% vs. 16.0% in group A & B) and photosensitivity (4.0% vs. 16.0% in group A & B) was predominant in group B. The difference was statistically significant (p=0.029). Whereas, erythema and burning was predominant in group A. Mean burning was found 0.15±0.08 in group A and 0.11±0.05 in group B and mean scaling was found 1.27±0.98 in group A and 1.45±0.98 in group B which were statistically non significant (p>0.05) between two groups. At 4th follow up mean total safety score was found 3.05±0.92 in group A and 4.65±1.25 in group B. Conclusion: Isotretinoin was as effective as lymecycline for the treatment of moderately severe acne vulgaris. Both treatments were well tolerated & effective. J Dhaka Med Coll. 2023; 32(1) : 63-70

S2k guideline for the treatment of hidradenitis suppurativa / acne inversa - Short version.

The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ±9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method.

High Efficacy of Oral Tetracyclines in Prosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention (DAIR) or Resection Arthroplasty With Destination Spacer Placement.

Prosthetic joint infections are often managed with debridement and implant retention (DAIR) or resection arthroplasty with destination spacer placement. Both surgical approaches require long courses of postoperative antibiotics, for which tetracycline antibiotics have not been well-studied. In this retrospective case series, we included patients at our institution treated for staphylococcal prosthetic joint infection managed with DAIR or destination spacer placement who were switched from IV antibiotics to oral tetracycline within 12 weeks of surgery. Our primary outcome of interest was treatment failure within one year of initial surgery. Among the patients in our series, 88.2% (n = 15) of patients who underwent DAIR and 100% (n = 7) of patients who underwent resection arthroplasty with destination spacer remained event-free for one year. These results demonstrated that the use of oral tetracyclines as long-term therapy in the treatment of these infections was effective and well-tolerated.

Minocycline and Diacetyl Minocycline Eye Drops Reduce Ocular Neovascularization in Mice.

To evaluate the efficacy of minocycline and a novel, modified minocycline analogue that lacks antimicrobial action, diacetyl minocycline (DAM), on choroidal neovascularization (CNV) in mice of both sexes. CNV was induced via laser injury in female and male C57BL/6J mice. Minocycline, DAM, or saline was administered via topical eye drops twice a day for 2 weeks starting the day after laser injury. CNV volume was measured using immunohistochemistry labeling and confocal microscopy. Minocycline reduced lesion volume by 79% (P ≤ 0.0004) in female and male mice. DAM reduced lesion volume by 73% (P ≤ 0.001) in female and male mice. There was no significant difference in lesion volume between minocycline and DAM treatment groups or between female and male mice. Both minocycline and DAM eye drops significantly reduced laser-induced CNV lesion volume in female and male mice. While oral tetracyclines have been shown to mitigate pathologic neovascularization in both preclinical studies and clinical trials, the present data are the first to suggest that tetracycline derivatives may be effective to reduce pathologic CNV when administered via topical eye drops. However, the action is unrelated to antimicrobial action. Targeted delivery of these medications via eye drops may reduce the potential for systemic side effects. Topical administration of minocycline and/or DAM via eye drops may represent a novel therapeutic strategy for disorders involving pathologic CNV.

Seasonal Patterns in Tetracycline-Associated Hyperpigmentation Among Patients With Acne Vulgaris.

Oral tetracyclines (TCNs) are commonly prescribed for acne, but they have been shown to increase the risk of hyperpigmentation, particularly in the setting of sun exposure. We evaluated seasonal trends in TCN-associated hyperpigmentation incidence in addition to Google search trends for hyperpigmentation-related terms. We performed a retrospective review of acne patients seen at Massachusetts General Brigham and Women’s Hospital between 1992 and 2022. We calculated the incidence of new hyperpigmentation diagnoses for each drug cohort. We also analyzed search volume of hyperpigmentation-related terms extracted from Google Trends. Seasonal differences in new hyperpigmentation diagnoses were identified among acne patients prescribed doxycycline (P=0.016), with peak incidence in April. In the control group of patients who had never received a TCN, diagnoses peaked in May. There were no significant seasonal differences among patients prescribed minocycline (P=0.885). There was greater search volume for hyperpigmentation-related terms in spring and summer compared to fall and winter (P<0.001). Limitations of this study include its retrospective nature and reliance on prescription and diagnosis coding data. Our findings support the seasonal periodicity of acne-related hyperpigmentation, underscoring the importance of photoprotection counseling for patients with acne. Additionally, doxycycline may be associated with an earlier onset of hyperpigmentation, suggesting a potential benefit of considering minocycline or other alternatives to doxycycline. J Drugs Dermatol. 2023;22(11):e9-e11    doi:10.36849/JDD.7409e.

Compatibility of Omadacycline With Select Parenteral Products in Simulated Y-site Administration

Omadacycline is a broad-spectrum intravenous and oral tetracycline antibiotic approved for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Available information on the compatibility of intravenous omadacycline is limited to sterile water, 0.9% sodium chloride, and 5% dextrose via a dedicated line. The objective of this work was to determine the intravenous compatibility of omadacycline with commonly used intravenous fluids and medications using simulated Y-site administration. Omadacycline was prepared at concentrations consistent with a maintenance dose (1 mg/mL) and a loading dose (2 mg/mL) with 0.9% sodium chloride according to the prescribing information. Compatibility via simulated Y-site administration was assessed with selected crystalloids (lactated Ringer's solution, magnesium sulfate, and normal saline with potassium chloride) and intravenous medications (bumetanide, furosemide, heparin, and insulin). Y-site administration was simulated by mixing 5 mL of omadacycline with 5 mL of each parenteral product prepared at standard concentrations for infusion. Compatibility was assessed by using visual, Tyndall beam, microscopy, and spectrophotometry methods at 0, 30, and 60 minutes. Omadacycline appeared physically compatible with lactated Ringer's solution, magnesium sulfate, normal saline with potassium chloride, bumetanide, heparin, and insulin at standard infusion concentrations. However, although the lower concentrations of omadacycline 1 mg/mL and furosemide 2 mg/mL showed compatibility, higher concentrations of either agent in combination resulted in incompatibility. Omadacycline appeared physically compatible with all products tested and incompatible with furosemide. Simultaneous administration of omadacycline with tested intravenous medications, except furosemide, is suggested to be safe.

Changes in the Anterior Segment and Dry Eye Parameters of People Using Oral Tetracycline

Aim: The purpose of the study is to evaluate the effect of anti-inflammatory efficiency of tetracycline on dry eye and anterior segment parameters. Material and Methods: This prospective study was conducted with 61 people who had been using tetracycline for the past 2 months. Each participant went through a detailed ophthalmological examination where intraocular pressure (IOP), central cornea thickness (CCT), K1 and K2 from keratometry measurements, anterior chamber depth (ACD), axial length (AXL), tear breakup time test (BUT), lissamin green staining (LG), Schirmer’s tear test-1 (ST) and ocular surface disease index (OSDI) score were evaluated. Measurements of the patients who would be using a daily dose of 100 mg doxycycline for 2 months were done prior to the medication as well as 1 month and 2 months after the medication. 3 data sets of the participants were compared at the end of 2 months. Results: When results were compared, it was found that ST and LG parameters gradually increased in the first and second months and this increase was statistically significant (p<0.001 and p=0.018, respectively). On the other hand, BUT and OSDI scores decreased over time but it was not statistically significant. There were no statistically significant differences in terms of other parameters either (p>0.05). When female and male participants were compared in terms of BUT, it was found that the decrease in females at the second month was higher and this was statistically significant (p=0.01). Conclusion: t was concluded that the young individuals using tetracycline displayed an early stage of improvement in dry eye parameters.

Factors Affecting Endogenous Oxalate Synthesis and Its Excretion in Feces and Urine in Rats

It has been observed that the feces as well as urine of rats fed diets supplemented with 3% glycine and 5.2% hydroxyproline contain unexpectedly high amounts of endogenously formed oxalate. That intestinal microorganisms do not synthesize significant amounts of oxalate was indicated by the findings that oral tetracycline had no effect on oxalate excretion and that germ-free rats excreted more oxalate than conventional rats. Since little intraperitoneally injected [14C]oxalate appeared in the feces, and rat intestinal mucosa homogenates were found to produce oxalate from a variety of precursors of which glyoxylic acid was by far the most important, it is probable that the intestinal mucosa may be an important source of fecal oxalate observed in these studies. Ninety percent of weanling rats fed complete diets supplemented with glycine and hydroxyproline developed urinary stones in 38 days. It has been concluded that in the treatment of patients with histories of calcium oxalate urolithiasis, more concern than is commonly shown should be directed towards the feeding of diets high in precursors of endogenous oxalate synthesis.oxalate hydroxyproline calculi

Acanthus ilicifolius Methanolic Extract for Oral Candidiasis Treatment through Tongue Epithelial STAT3 and Cell Death Evaluation.

This study aimed to evaluate the effects of topical application of Acanthus ilicifolius methanolic extract on signal transducer and activator of transcription 3 (STAT3) expression and tongue epithelial cell death caused by oral candidiasis under immunosuppressive conditions. To obtain the oral candidiasis model, 20 healthy male Rattus norvegicus (Wistar) rats were administered oral dexamethasone and tetracycline for 14 days and oral candidiasis was induced with Candida albicans (ATCC-10231) 1 McFarland. They were then randomized into four groups-immunosuppression (K-), oral candidiasis (K + ), nystatin treatment (P1), and 20% A. ilicifolius methanolic extract treatment (P2) and were treated for 14 days. Histological analyses of cell death and candida invasion and immunohistochemical analysis of STAT3 in epithelial cells were performed. Epithelial cell death data were analyzed using one-way analysis of variance (ANOVA) and the post hoc Games-Howell test (p < 0.05) and STAT3 expression with one-way ANOVA and the post hoc least significant difference test (p < 0.05). Cell death was significantly different between K- and K+ and between K+ and P1 and P2 (p < 0.05); there were no significant differences between K- and P1 and P2 and between P1 and P2 (p > 0.05). STAT3 expression was significantly different between K- and P1 and P2 and between K+ and P1 and P2 (p < 0.05), but there were no significant differences between K+ and K- and between P1 and P2 (p > 0.05). Topical administration of A. ilicifolius methanol extract increased STAT3 expression and decreased tongue epithelial cell death caused by oral candidiasis.

Mucous membrane pemphigoid - a report of four cases

Introduction. Mucous membrane pemphigoid (MMP) is a rare autoimmune, chronic inflammatory disease that affects mucous membranes, most commonly the eyes and mouth, with or without skin involvement. It is a complex disease with several complications, including scarring, especially on conjunctival mucosa, that can lead to visual loss. Case report. We report four patients (two men and two women) with MMP. In all patients, the disease started between seventy and eighty years of age. The diagnosis was confirmed based on clinical appearance, histology, direct and indirect immunofluorescence studies, indirect split skin technique, and enzyme-linked immunosorbent assay (ELISA) test. The majority of lesions were on the gums and buccal mucosa; one patient had laryngeal involvement and a lesion on the umbilicus. No ocular involvement and no malignancy were detected. Direct immunofluorescence tests revealed continuous linear IgG deposition in the basal membrane zone in two patients, and they were treated with oral nicotinamide and tetracycline hydrochloride. In two patients, we detected IgG along with IgA linear deposition; they received treatment with methylprednisolone. Complete remission was achieved in all patients. Conclusion. Early diagnosis and an adequate therapeutic approach are necessary for the MMP treatment in long-term disease control and reduction of disease-related complications.

Changes inStreptococcus pneumoniaeSusceptibility in Wisconsin: Implications for Clinical Treatment Decisions for Respiratory Infections

Objective: In 2019, the American Thoracic Society and Infectious Diseases Society of America updated clinical practice guidelines for community-acquired pneumonia (CAP). In contrast to guidelines published in 2007, macrolide monotherapy for outpatients was made a conditional recommendation based on resistance levels. Local knowledge of current antimicrobial susceptibility is needed to guide management of CAP and other bacterial respiratory pathogens. The purpose of this study was to investigate antimicrobial susceptibility profiles and trending for Wisconsin Streptococcus pneumoniae isolates.Design: Multi-center laboratory surveillance, with testing at a central location utilizing standardized susceptibility testing protocols.Methods: Data published by the Wisconsin Department of Health Services (DHS) were augmented with data from the Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program. Data were stratified by invasive or non-invasive sources, as well as DHS region and compared to data compiled from 2006-2010.Results: Susceptibility rates for ≥ 916 invasive S. pneumoniae assessed from 2016-2020 were greater than 91% for ceftriaxone, tetracycline, and fluoroquinolone agents and were generally higher than those from 354 non-invasive isolates. Low susceptibility rates were observed for invasive isolates of penicillin (78.7%) and erythromycin (64.8%) and were even lower for non-invasive isolates (73.8% and 59.9%, respectively). This erythromycin susceptibility rate was a significant reduction from that observed in 2006-2010 (80.4; P < 0.0002). 24.8% of isolates generated an erythromycin MIC ≥ 8 μg/mL. Statewide geographic variability was noted.Conclusions: Rates of S. pneumoniae susceptibility to parenteral penicillins and cephems, and oral tetracycline and fluoroquinolone agents, remain high throughout Wisconsin. However, low oral penicillin susceptibility rates, taken together with declining macrolide susceptibility rates, should cause clinicians to consider alternative treatment options for respiratory tract infections, especially with macrolides.

A systematic review and network meta-analysis of topical pharmacological, oral pharmacological, physical and combined treatments for acne vulgaris.

Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity. To identify best treatments for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features. We undertook a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, published up to May 2020. Outcomes included percentage change in total lesion count from baseline, treatment discontinuation for any reason, and discontinuation owing to side-effects. Risk of bias was assessed using the Cochrane risk-of-bias tool and bias adjustment models. Effects for treatments with ≥ 50 observations each compared with placebo are reported below. We included 179 RCTs with approximately 35 000 observations across 49 treatment classes. For mild-to-moderate acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with benzoyl peroxide (BPO) [mean difference 26·16%, 95% credible interval (CrI) 16·75-35·36%]; physical - chemical peels, e.g. salicylic or mandelic acid (39·70%, 95% CrI 12·54-66·78%) and photochemical therapy (combined blue/red light) (35·36%, 95% CrI 17·75-53·08%). Oral pharmacological treatments (e.g. antibiotics, hormonal contraceptives) did not appear to be effective after bias adjustment. BPO and topical retinoids were less well tolerated than placebo. For moderate-to-severe acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with lincosamide (clindamycin) (44·43%, 95% CrI 29·20-60·02%); oral pharmacological - isotretinoin of total cumulative dose ≥ 120 mg kg-1 per single course (58·09%, 95% CrI 36·99-79·29%); physical - photodynamic therapy (light therapy enhanced by a photosensitizing chemical) (40·45%, 95% CrI 26·17-54·11%); combined - BPO with topical retinoid and oral tetracycline (43·53%, 95% CrI 29·49-57·70%). Topical retinoids and oral tetracyclines were less well tolerated than placebo. The quality of included RCTs was moderate to very low, with evidence of inconsistency between direct and indirect evidence. Uncertainty in findings was high, in particular for chemical peels, photochemical therapy and photodynamic therapy. However, conclusions were robust to potential bias in the evidence. Topical pharmacological treatment combinations, chemical peels and photochemical therapy were most effective for mild-to-moderate acne. Topical pharmacological treatment combinations, oral antibiotics combined with topical pharmacological treatments, oral isotretinoin and photodynamic therapy were most effective for moderate-to-severe acne. Further research is warranted for chemical peels, photochemical therapy and photodynamic therapy for which evidence was more limited. What is already known about this topic? Acne vulgaris is the eighth most common disease globally. Several topical, oral, physical and combined treatments for acne vulgaris exist. Network meta-analysis (NMA) synthesizes direct and indirect evidence and allows simultaneous inference for all treatments forming an evidence network. Previous NMAs have assessed a limited range of treatments for acne vulgaris and have not evaluated effectiveness of treatments for moderate-to-severe acne. What does this study add? For mild-to-moderate acne, topical treatment combinations, chemical peels, and photochemical therapy (combined blue/red light; blue light) are most effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy (light therapy enhanced by a photosensitizing chemical) are most effective. Based on these findings, along with further clinical and cost-effectiveness considerations, National Institute for Health and Care Excellence (NICE) guidance recommends, as first-line treatments, fixed topical treatment combinations for mild-to-moderate acne and fixed topical treatment combinations, or oral tetracyclines combined with topical treatments, for moderate-to-severe acne.

A pilot retrospective study on trichoscopy of 21 cases of rosacea of the scalp

To the Editor: Rosacea is a common photodermatosis affecting up to 18% of the population. 1 Hampton P.J. Berth-Jones J. Duarte Williamson C.E. et al. British Association of Dermatologists guidelines for the management of people with rosacea 2021. Br J Dermatol. 2021; 185: 725-735https://doi.org/10.1111/BJD.20485 Crossref PubMed Google Scholar Only few reports on rosacea of the scalp, also known as red scalp disease (RSD) have been published. 2 Oberholzer P.A. Nobbe S. Kolm I. Kerl K. Kamarachev J. Trüeb R.M. Red scalp disease–a rosacea-like dermatosis of the scalp? Successful therapy with oral tetracycline. Dermatology. 2009; 219: 179-181https://doi.org/10.1159/000228319 Crossref PubMed Scopus (13) Google Scholar ,3 Vázquez-Herrera N.E. Zamora-Benze D.M. Garza-Chapa J.I. Rodríguez-Baca A.B. Tosti A. Scalp rosacea: rethinking peripilar scaling. Skin Appendage Disord. 2021; 7: 382-386https://doi.org/10.1159/000514565 Crossref PubMed Scopus (0) Google Scholar Based on our experience, its prevalence might be higher because the clinical features of burning, itching, and sensitive scalp overlap with other scalp dermatoses.

A plethora of ocular surface manifestations in a multidisciplinary ocular graft-versus-host disease unit

To describe the experience in a recently created ocular graft-versus-host disease unit in a tertiary hospital and to detail ocular surface features and complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study included all patients who underwent allo-HSCT, with or without chronic GVHD and were being monitored in the Hematopoietic Stem Cell Transplantation Unit in the UNICAMP Clinical Hospital (Campinas, Sao Paulo, Brazil) from 2015 to 2020. Patients were concomitantly evaluated by hematology and ophthalmology teams of the Ocular GVHD Unit. Hematologists performed a comprehensive systemic evaluation searching and grading mouth, skin, lungs, gastrointestinal tract, liver and genitalia GVHD. While ophthalmologists evaluated ocular symptoms through specific questionnaire (Ocular Surface Disease Index—OSDI) and a protocol of distinct ocular surface parameters for dry eye disease (1) and ocular complications, which encompassed meniscometry, non-invasive tear break-up time (NITBUT) measurement, conjunctival hyperemia quantification, meibography, fluorescein and lissamine staining and Schirmer’s test. Patients were diagnosed with chronic GVHD using the National Institutes of Health (NIH) Consensus Criteria for Chronic Graft-versus-Host Disease. The International Chronic Ocular GVHD Consensus Group (ICOGCG) score was obtained at the onset of ocular disease presentation or afterwards. A total of 82 patients underwent allo-HSCT (97.6% full matched and 2.4% haploidentical), mainly for cases of leukemia and 73.2% had chronic GVHD. Mean onset time for chronic GVHD was 232 ± 7.75 days. The mouth, skin, and eyes were the main organs involved (63%, 50%, and 48%, respectively). Symptom scores and all ocular surface parameters differ in patients with and without chronic GVHD and along different timepoints of the follow-up. Ocular complications mostly involved were severe DED and meibomian gland dysfunction, conjunctival scarring, cataract and infections resulting in keratitis and corneal perforation. As therapeutic strategies, 73% patients received preservative-free lubricants, 27% autologous serum, 48% topical steroids, 27% oral tetracycline derivatives, 22% mucolytic eye drops and 3 patients needed bandage contact lens. Ocular GVHD is a complex and challenging disease with varied manifestations, resulting in a broad range of ocular test endpoints, and inconsistent treatment responses. The main ocular presentations were dry eye, meibomian gland dysfunction and cataracts. The therapeutic approach often involves topical steroids and autologous serum tears. It is important to monitor these patients closely, so the ocular GVHD Unit may improve the care, providing prompt identification of ocular manifestations and faster treatment of complications.

34741 The keto rash: Case report and literature review of prurigo pigmentosa induced by a ketogenic diet

Prurigo pigmentosa (PP) is a rare inflammatory dermatosis of unknown etiology that primarily affects adolescents and young adults. It is typically characterized by a pruritic eruption of erythematous papules on the trunk and neck that evolves into reticulate hyperpigmentation upon resolution of the inflammatory phase of the rash. It has been associated with various triggers, including the metabolic state of ketosis. Interestingly, the recent increase in popularity of the ketogenic diet for weight loss has led to an increased number of PP cases reported in the literature. We present a case of PP in a 21-year-old Hispanic male, which erupted during strict adherence to a ketogenic diet. We conducted a literature review and identified 19 other cases of PP related to ketogenic diet. While this condition has historically been reported primarily in Asia, we found cases occurring in patients of Middle Eastern, Caucasian, Hispanic, Asian, and African descent. On average, the rash presented 31 days after initiating the diet and subsided 18 days after diet cessation. Most cases were treated with an oral tetracycline and resolved with residual hyperpigmentation. We present this information to highlight the increasing association of PP with the ketogenic diet. Dermatologists should be aware of the timing of rash onset and resolution in relation to the diet, in order to improve the early diagnosis and treatment of this preventable dermatosis and improve patient outcomes.

Antibiotic Resistance Risk with Oral Tetracycline Treatment of Acne Vulgaris.

Almost 1 billion people worldwide have acne, and oral tetracyclines, including doxycycline and minocycline, are effective and frequently prescribed treatments for acne. However, there is growing concern for the development of antibiotic resistance with such widespread utilization by dermatologists. Additionally, tetracyclines are known to have various potential side effects, including gut dysbiosis, gastrointestinal upset, photosensitivity, dizziness, and vertigo. However, in 2018 a novel narrow-spectrum tetracycline, sarecycline, was Food and Drug Administration-approved to treat moderate-to-severe acne vulgaris in patients 9-years-old and above. Sarecycline was designed to target Cutibacterium acnes, the pathogenic bacterium in acne vulgaris, which may reduce the risk of resistance. This paper examines the growing concerns of antibiotic resistance due to oral tetracycline usage in the treatment of acne vulgaris, with a focus on the promising third-generation, narrow-spectrum tetracycline, sarecycline.

Acneiform eruptions with combination targeted cancer therapy in colorectal cancer patients.

Epidermal growth factor receptor inhibitors (EGFRI) can be used with pathway inhibitors, including mitogen-activated protein kinase kinase inhibitors (MEKIs), BRAF inhibitors (BRAFIs), and checkpoint inhibitors such as programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) to treat colorectal cancer. These can precipitate treatment-resistant acneiform eruptions, prompting dose modification or discontinuation. Predicting the likelihood of severe rash development and crafting effective treatments may promote adherence to life-saving chemotherapy. An Institutional Review Board-approved retrospective chart review of patients with colorectal cancer treated with EGFRI or MEKI in combination with HER2, BRAF, PI3K, or checkpoint inhibitors between January 1, 2016, and January 1, 2020, was performed. Surrogates for rash severity were investigated, including lower extremity involvement, utilization of oral steroids or retinoids, dose modification, and incidence of superinfection. Of 122 patients treated with combination therapy, 105 developed a rash, and 87 developed an acneiform eruption. Common combinations included MEKI/PD-LI, EGFRI/MEKI, and MEKI/PD-1I. Patients treated with EGFRI/MEKI developed the most severe rashes (p = 0.02). Lower extremity involvement was more frequent with EGFRI/MEKI compared to alternative combinations (p = 0.05). Drug holiday correlated with all rash severity surrogates, including rash grade, lower extremity involvement, oral steroid or retinoid use, and incidence of superinfection. Use of oral steroids or retinoids was associated with development of superinfection (p = 0.002). Prophylactic tetracycline use did not impact rash severity or rash incidence. This is the first descriptive analysis to characterize acneiform eruptions for patients with colorectal cancer on combination cancer therapy. Approximately 85% of patients developed a cutaneous toxicity with what appears to be synergistic effects of EGFRI and MEKI combination therapy causing the most severe eruptions. Superinfection rate correlated to systemic therapy use beyond oral tetracyclines. Further investigation into the utility of prophylactic oral tetracyclines in this population is needed.

Prevention and management of acneiform rash associated with EGFR inhibitor therapy: A systematic review and meta-analysis.

Epidermal growth factor receptor (EGFR) inhibitors are established therapies for advanced lung, colorectal, and head and neck cancers. They commonly cause acneiform eruptions that affect patient quality of life and may lead to discontinuation of therapy. A systematic review and meta-analysis was undertaken to assess strategies for the prevention and reactive management of acneiform rash associated with EGFR inhibitor therapy for advanced lung, colorectal, and head and neck cancers. A systematic Medline, Embase, and EBM Reviews database search was conducted on the 2nd of January 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed and the studies were critically appraised. Studies were selected if they focused on preventing or treating acneiform eruptions in adults being treated for advanced lung cancer, colorectal cancer, and head and neck cancers with EGFR inhibitors. Oral antibiotics had the greatest efficacy in preventing grade 2 or higher acneiform eruptions with a relative risk reduction of 40% (RR=.6, 95% CI .46-.79, p<.01). Other treatment modalities did not have statistically significant results. Topical antibiotics had a total relative risk reduction of 19% (RR=.81, 95% CI .45-1.48, p=.5). Vitamin K1 cream did not reduce the relative risk (RR=1.08, 95% CI .45-1.48, p=.50). Sunscreen had a total relative risk reduction of 25% (RR=.75, 95% CI .49-1.14, p=.18). The results of this meta-analysis reinforce the fact that oral tetracycline antibiotics are the most efficacious prophylactic option for acneiform eruptions in EGFR inhibitors. They should be offered to suitable patients commencing treatment and used with a general skin-care routine involving emollients and avoidance of irritants.

A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora.

ObjectivesThere is interest in doxycycline as prophylaxis against sexually transmitted infections (STIs), but concern about antimicrobial resistance (AMR). We conducted a systematic review (CRD42021273301) of the impact of oral tetracycline-class antibiotics on AMR in normal flora.MethodsWe searched MEDLINE, EMBASE, the Cochrane Library (1940–2021) and conference proceedings (2014–21) for randomized controlled trials in adults comparing daily oral tetracycline-class antibiotics to non-tetracycline controls. The primary outcome was AMR to tetracyclines; secondary outcomes included resistance to non-tetracyclines. Data were inappropriate for meta-analysis, so we analysed findings descriptively.ResultsOur search yielded 6265 abstracts of which 7 articles fulfilled inclusion criteria. Most were at moderate/high risk of bias, generally due to inadequate methodologic reporting. Studies used doxycycline, tetracycline, oxytetracycline or minocycline for 2–18 weeks. Most observed an increased burden of tetracycline resistance, including in subgingival (n = 3 studies), gastrointestinal (n = 2) and upper respiratory tract (n = 1) flora; one study of skin flora found no change in tetracycline-resistant Propionibacterium species after 18 weeks of oxytetracycline/minocycline. Four studies reassessed AMR at 2–50 weeks post-intervention and reported varying degrees of resistance. Three articles reported on the prevalence of non-tetracycline AMR after doxycycline prophylaxis, of which one found a transient increase among gastrointestinal Escherichia coli; the other two showed no difference from control.ConclusionsAlthough the effects are modest and transient, limited data from small prospective studies may suggest that oral tetracyclines for 2–18 weeks increase resistance in subgingival, gastrointestinal and upper respiratory tract flora. STI prophylaxis trials should include AMR in commensal bacteria as study outcomes.

Efficacy of non-surgical monotherapies for hidradenitis suppurativa: a systematic review and network meta-analyses of randomized trials

Objective We determined the relative efficacy of non-surgical monotherapies for hidradenitis suppurativa (HS). Methods Network meta-analyses were conducted to determine treatments’ surface under the cumulative ranking curve (SUCRA) value (i.e. an estimate that ranks efficacy); pairwise comparisons were conducted. Results and conclusions Ten trials were eligible for quantitative analyses; however, all did not have a common endpoint. Outcomes corresponded to pain severity, clinical response, quality of life and abscess count. For pain reduction, infliximab was ranked most efficacious (SUCRA = 94%) compared to bermekimab, anakinra and placebo; infliximab reduced pain more significantly (p < .05) than anakinra and then placebo. For the occurrence of clinical response, bimekizumab had the highest SUCRA (67%) relative to adalimumab, anakinra and placebo; bimekizumab was more efficacious than placebo (p < .05). For the quality of life in mild HS, Botox had the highest SUCRA (94%) compared to adalimumab and placebo; Botox was more efficacious than placebo (p < .05). For reduction in abscess count, oral tetracycline had the highest SUCRA (48%) compared to topical clindamycin and vehicle. Our work—being the first NMA study on non-surgical HS monotherapies—contributes to the comparative effectiveness literature for this condition.