-
The Cochrane Database of Systematic... Aug 2023Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.
OBJECTIVES
To assess the effects of treatments for bullous pemphigoid.
SEARCH METHODS
We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.
MAIN RESULTS
We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.
AUTHORS' CONCLUSIONS
Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.
Topics: Humans; Azathioprine; Prednisone; Clobetasol; Pemphigoid, Bullous; Doxycycline; Methylprednisolone; Dapsone; Niacinamide
PubMed: 37572360
DOI: 10.1002/14651858.CD002292.pub4 -
The Medical Letter on Drugs and... Feb 2024
Topics: Humans; Acne Vulgaris
PubMed: 38294764
DOI: 10.58347/tml.2024.1695a -
Clinical Science (London, England :... Aug 2023Abdominal aortic aneurysm (AAA) is a severe vascular disease and a major public health issue with an unmet medical need for therapy. This disease is featured by a... (Review)
Review
Abdominal aortic aneurysm (AAA) is a severe vascular disease and a major public health issue with an unmet medical need for therapy. This disease is featured by a progressive dilation of the abdominal aorta, boosted by atherosclerosis, ageing, and smoking as major risk factors. Aneurysm growth increases the risk of aortic rupture, a life-threatening emergency with high mortality rates. Despite the increasing progress in our knowledge about the etiopathology of AAA, an effective pharmacological treatment against this disorder remains elusive and surgical repair is still the unique available therapeutic approach for high-risk patients. Meanwhile, there is no medical alternative for patients with small aneurysms but close surveillance. Clinical trials assessing the efficacy of antihypertensive agents, statins, doxycycline, or anti-platelet drugs, among others, failed to demonstrate a clear benefit limiting AAA growth, while data from ongoing clinical trials addressing the benefit of metformin on aneurysm progression are eagerly awaited. Recent preclinical studies have postulated new therapeutic targets and pharmacological strategies paving the way for the implementation of future clinical studies exploring these novel therapeutic strategies. This review summarises some of the most relevant clinical and preclinical studies in search of new therapeutic approaches for AAA.
Topics: Humans; Aortic Aneurysm, Abdominal; Aorta, Abdominal; Doxycycline; Aortic Rupture; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 37559446
DOI: 10.1042/CS20220795 -
The American Surgeon Nov 2023Esophageal and gastric mucosal injuries are well-documented adverse effects of doxycycline leading to odynophagia, chest pain, and abdominal pain. There are no clear...
Esophageal and gastric mucosal injuries are well-documented adverse effects of doxycycline leading to odynophagia, chest pain, and abdominal pain. There are no clear diagnostic criteria for such adverse effects; hence, the diagnosis depends heavily on thorough history. There is a paucity of literature describing life-threatening complications from doxycycline-induced mucosal injury, such as hemorrhage and perforation. We present the first case report describing a gastric perforation from doxycycline use.
Topics: Humans; Doxycycline; Stomach Diseases; Esophagus; Gastric Mucosa; Chest Pain; Iatrogenic Disease; Thoracic Injuries
PubMed: 34551605
DOI: 10.1177/00031348211047494 -
Ugeskrift For Laeger Oct 2023Scrub typhus is caused by the mite-borne bacterium Orientia tsutsugamushi. Imported cases have been suspected in Denmark but no diagnostic method has yet been available...
Scrub typhus is caused by the mite-borne bacterium Orientia tsutsugamushi. Imported cases have been suspected in Denmark but no diagnostic method has yet been available to confirm the diagnosis. This is a case report of a 38-year-old male admitted to hospital with high fever, severe malaise and headache after returning from Malaysia. Scrub typhus was suspected and the patient recovered after one week of doxycycline treatment. The pathogen was identified by use of microbiome 16S/18S rRNA next-generation sequencing on ethylenediamine tetraacetic acid (EDTA) blood, which in the future may serve an important role in the investigation of travel-associated infections.
Topics: Male; Humans; Adult; Orientia tsutsugamushi; Scrub Typhus; Travel; Doxycycline; Travel-Related Illness; RNA, Ribosomal, 16S
PubMed: 37873999
DOI: No ID Found -
Radiology Feb 2024A 15-year-old boy presented with a 3-week history of inner left thigh pain provoked by activity and experienced occasionally at rest. He denied nighttime pain, fever, or...
A 15-year-old boy presented with a 3-week history of inner left thigh pain provoked by activity and experienced occasionally at rest. He denied nighttime pain, fever, or chills. Laboratory investigation revealed the following normal values: hemoglobin level of 15.6 g/dL (normal range, 13-16 g/dL), platelet count of 240 × 10/µL (normal range, 140-440 × 10/µL), and total leukocyte count of 7100 cells/µL (normal range, 4500-11 000 cells/µL). The percentage of neutrophils was considered low at 44% (normal range, 54%-62%), and the percentage of eosinophils was slightly high at 3.7% (normal range, 0%-3%). An anteroposterior radiograph of the left hip is shown (Fig 1). Physical therapy was initiated, with no improvement after 2 weeks of therapy. The patient was referred to an orthopedist for further evaluation. On physical examination, the patient endorsed marked left hip pain with hip flexion to 90°, limited internal and external rotation (5° and 15°, respectively), and antalgic gait favoring the left leg. Hip MRI (Fig 2) and further serologic analysis were requested for further evaluation. Although the serologic testing was performed at an outside laboratory, the physician reported positive immunoglobulin-G Lyme titers, normal C-reactive protein level, and normal erythrocyte sedimentation rate. Pelvic CT was requested (Fig 3). The patient was prescribed a course of doxycycline (100 mg twice daily for 28 days), with reported resolution of symptoms 2 weeks after initiation of treatment. Three weeks later, he presented to our department with recurrent left hip pain, which was similar in severity compared with initial presentation. A second MRI of the left hip was performed 4 months after initial presentation (Fig 4).
Topics: Male; Humans; Adolescent; Arthralgia; Pain; Cognition; Doxycycline; Fever
PubMed: 38411515
DOI: 10.1148/radiol.230628 -
JAMA Oct 2023
PubMed: 37738283
DOI: 10.1001/jama.2023.16416 -
American Journal of Respiratory and... Sep 2023Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term... (Randomized Controlled Trial)
Randomized Controlled Trial
Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes. To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD. People with moderate to very severe COPD and an exacerbation history were recruited from three UK centers and randomized to 12 months of doxycycline 100 mg once daily or placebo. The primary study outcome was the exacerbation rate per person-year. A total of 222 people were randomized. Baseline mean FEV was 1.35 L (SD, 0.35 L), 52.5% predicted (SD, 15.9% predicted). The median number of treated exacerbations in the year before the study was 2 (SD, 1-4). A total of 71% of patients reported two or more exacerbations, and 81% were already prescribed inhaled corticosteroids at baseline. The COPD exacerbation rate did not differ between the groups (doxycycline/placebo rate ratio [RR], 0.86; 95% confidence interval [CI], 0.67-1.10; = 0.23). No difference was seen if only treated exacerbations or hospitalizations were considered. In preplanned subgroup analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR, 0.36; 95% CI, 0.15-0.85; = 0.019) and in those with an eosinophil count <300 cells/μl (RR, 0.50; 95% CI, 0.29-0.84; = 0.01). Health status measured by St. George's Respiratory Questionnaire was 5.2 points worse in the doxycycline group at 12 months ( < 0.007). Doxycycline did not significantly reduce the exacerbation rate, over 12 months, in participants with COPD who exacerbated regularly, but it may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/μl. Clinical trial registered with www.clinicaltrials.gov (NCT02305940).
Topics: Humans; Doxycycline; Anti-Bacterial Agents; Eosinophils; Adrenal Cortex Hormones; Pulmonary Disease, Chronic Obstructive; Double-Blind Method; Disease Progression
PubMed: 37450935
DOI: 10.1164/rccm.202212-2287OC -
Parasites & Vectors Jul 2023Since the advent of ivermectin (along with melarsomine and doxycycline), heartworm has come to be viewed as a solved problem in veterinary medicine, diminishing... (Review)
Review
Since the advent of ivermectin (along with melarsomine and doxycycline), heartworm has come to be viewed as a solved problem in veterinary medicine, diminishing investment into non-clinical research on Dirofilaria immitis. However, heartworm infections continue to pose problems for practitioners and their patients and seem to be increasing in frequency and geographic distribution. Resistance to preventative therapies (macrocyclic lactones) complicates the picture. The use of chemotherapy for other kinds of pathogens has benefitted enormously from research into the basic biology of the pathogen and on the host-pathogen interface. A lack of basic information on heartworms as parasites and how they interact with permissive and non-permissive hosts greatly limits the ability to discover new ways to prevent and treat heartworm disease. Recent advances in technical platforms will help overcome the intrinsic barriers that hamper research on D. immitis, most notably, the need for experimentally infected dogs to maintain the life cycle and provide material for experiments. Impressive achievements in the development of laboratory animal models for D. immitis will enhance efforts to discover new drugs for prevention or treatment, to characterize new diagnostic biomarkers and to identify key parasite-derived molecules that are essential for survival in permissive hosts, providing a rational basis for vaccine discovery. A 'genomics toolbox' for D. immitis could enable unprecedented insight into the negotiations between host and parasite that enable survival in a permissive host. The more we know about the pathogen and how it manipulates its host, the better able we will be to protect companion animals far into the future.
Topics: Humans; Animals; Dogs; Dirofilaria immitis; Dog Diseases; Dirofilariasis; Ivermectin; Lactones
PubMed: 37480077
DOI: 10.1186/s13071-023-05762-9 -
The New England Journal of Medicine May 2024
Topics: Animals; Humans; Male; Elephantiasis, Filarial; Filaricides; Wuchereria bancrofti; Aged; Treatment Outcome; Doxycycline; Albendazole; Diethylcarbamazine; Edema; Penis; Scrotum; Leg; Magnetic Resonance Imaging
PubMed: 38708851
DOI: 10.1056/NEJMicm2313316