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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 -
Clinical Oral Investigations Dec 2023The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment. (Review)
Review
OBJECTIVE
The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment.
MATERIALS AND METHODS
This review was conducted according to PRISMA-ScR guidelines and registered at PROSPERO (CRD42021243524). Consulted databases were Pubmed, Embase, Scopus, and Web of Science. The inclusion criteria was as follows: clinical trials, case series, prospective, and retrospective studies conducted with participants presenting OLP of any sex and age.
RESULTS
Thirty-two studies were selected, assessing 9 different SNSI: methotrexate, dapsone, levamisole, hydroxychloroquine, thalidomide, metronidazole, azathioprine, mycophenolate mofetil, and colchicine. Methotrexate and dapsone were the drugs with the best evidence among the options included, regarding number and quality of studies. Methotrexate resulted in significant improvement in the clinical condition and remission of symptoms, ranging between 63 and 93% of cases. Dapsone presented a similar effect to the use of topical corticosteroids and tacrolimus CONCLUSION: Among SNSI therapeutic options, methotrexate, and dapsone showed promising efficacy and safety. However, large-scale randomized clinical trials are still needed.
CLINICAL RELEVANCE
SNSI have been used in the treatment of recalcitrant OLP; however, so far, it is not clear which are the best options. This scoping review highlights the potential use of methotrexate and dapsone.
Topics: Humans; Lichen Planus, Oral; Methotrexate; Prospective Studies; Retrospective Studies; Immunologic Factors; Adjuvants, Immunologic; Dapsone
PubMed: 37921879
DOI: 10.1007/s00784-023-05357-9 -
Dermatologie (Heidelberg, Germany) Sep 2023Pemphigoid diseases are a group of bullous autoimmune diseases characterized by autoantibodies against structural proteins of the dermal-epidermal junction. With... (Review)
Review
Pemphigoid diseases are a group of bullous autoimmune diseases characterized by autoantibodies against structural proteins of the dermal-epidermal junction. With a steadily growing aging population, pemphigoid diseases are emerging as a significant medical challenge, because they occur primarily in older individuals. The by far most common disease is bullous pemphigoid, which is clinically characterized by tense blisters, erosions, erythema or urticarial plaques, while severe pruritus is the leading subjective symptom. Mucous membrane pemphigoid predominantly affects surface-close mucous membranes with painful erosions and blisters as well as frequently scarring usually in the mouth, nose, and eyes. Anti-p200 pemphigoid clinically resembles bullous pemphigoid but is much less common. Diagnosis of these diseases involves the combination of clinical evaluation, lesional histopathology, direct immunofluorescence microscopy of a perilesional biopsy and serology. Topical and systemic corticosteroids are the mainstay of pemphigoid diseases treatment. Depending on the severity of the disease, various potentially corticosteroid-sparing therapies, such as dapsone, doxycycline, methotrexate, azathioprine and mycophenolate may be used. In severe courses, treatment with rituximab, cyclophosphamide, intravenous immunoglobulins or immunoadsorption are second- or third-line treatment options. Patients are best managed in centers experience with the management of pemphigoid diseases. Updated national and international guidelines for the diagnosis and treatment of bullous pemphigoid and mucous membrane pemphigoid have recently been published.
Topics: Humans; Aged; Pemphigoid, Bullous; Blister; Pemphigoid, Benign Mucous Membrane; Autoimmune Diseases; Immunosuppressive Agents
PubMed: 37594515
DOI: 10.1007/s00105-023-05209-3 -
Chinese Medical Journal Jul 2023
Topics: Humans; Dapsone; Drug Hypersensitivity; Hypersensitivity; Syndrome
PubMed: 37057725
DOI: 10.1097/CM9.0000000000002492 -
Cureus Dec 2023Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated... (Review)
Review
Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated poorly and had to face discrimination due to the gruesome disease's complications. , the bacterium causative of leprosy, can generally be found in the nine-banded armadillo. The bacterium is transmitted via aerosol droplets and broken skin-to-skin contact. Once M enters the body, it will target peripheral nerves and the lining mucosa of the skin and eyes, thus causing inflammation and tenderness of the affected area. Over time, this will lead to peripheral neuropathy and weakness of the affected body parts. Treatment of leprosy involves multi-drug combinations such as dapsone, rifampin, and clofazimine. Even though leprosy is curable, early detection and treatment are crucial to preventing irreversible damage and disabilities. Prevention measures include early detection, treatment regimen adherence, close contact prophylaxis, contact tracing, and community awareness. This review aims to provide the latest diagnostic and therapeutic recommendations for leprosy. It outlines the epidemiology, microbiology, clinical treatment, and immunological methods used to detect leprosy.
PubMed: 38179342
DOI: 10.7759/cureus.49954 -
International Journal of Gynaecology... Jun 2024The aim of this review is to increase obstetrician awareness of pregnancy-associated Sweet syndrome. Patients present with fever, leukocytosis, and skin eruption, which... (Review)
Review
The aim of this review is to increase obstetrician awareness of pregnancy-associated Sweet syndrome. Patients present with fever, leukocytosis, and skin eruption, which can mimic other infectious or inflammatory conditions, but do not respond to antibiotics. A search using PubMed, EMBASE, and Web of Science Core Collection was conducted to review all reported cases of pregnancy-associated Sweet syndrome, an acute febrile neutrophilic dermatosis occurring during pregnancy or postpartum. A total of 33 episodes among 30 patients were identified, with the majority (54.5% [18]) of cases occurring within the second trimester. Among the 30 patients, skin lesions most commonly affected the head and neck (73.3% [22]), with rare oral or ocular involvement. Leukocytosis was the most common laboratory finding, reported in 96.7% [29] of patients, with neutrophil predominance noted in 70.0% [21]. The diagnosis was confirmed for all patients with pathognomonic results of skin biopsies. Of the 27 cases detailing treatment, systemic corticosteroids were most frequently used (19 cases), followed by conservative management (seven cases), and dapsone (one case). The dapsone-treated patient and 15 of the 19 steroid-treated patients experienced resolution, but additional management strategies were required in the remaining four individuals. Spontaneous resolution occurred during pregnancy in six of the seven conservatively managed individuals, with one patient experiencing spontaneous abortion shortly after skin eruption at 10 weeks of gestation. No associated maternal deaths were reported. Obstetric complications of pregnancy-associated Sweet syndrome included endomyometritis, sterile placental abscesses, and abdominal wall necrosis. Delivery of healthy infants occurred in 24 of the 25 cases that presented fetal outcome, which included two infants who underwent medically indicated preterm deliveries.
PubMed: 38881204
DOI: 10.1002/ijgo.15713 -
European Journal of Medicinal Chemistry Dec 2023Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely,...
Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely, unwanted perforin activity can also result in auto-immune attack, graft rejection and aberrant responses to pathogens. Perforin is critical for the function of the granule exocytosis cell death pathway and is therefore a target for drug development. In this study, by screening a fragment library using NMR and surface plasmon resonance, we identified 4,4-diaminodiphenyl sulfone (dapsone) as a perforin ligand. We also found that dapsone has modest (mM) inhibitory activity of perforin lytic activity in a red blood cell lysis assay in vitro. Sequential modification of this lead fragment, guided by structural knowledge of the ligand binding site and binding pose, and supported by SPR and ligand-detected F NMR, enabled the design of nanomolar inhibitors of the cytolytic activity of intact NK cells against various tumour cell targets. Interestingly, the ligands we developed were largely inert with respect to direct perforin-mediated red blood cell lysis but were very potent in the context of perforin's action on delivering granzymes in the immune synapse, the context in which it functions physiologically. Our work indicates that a fragment-based, structure-guided drug discovery strategy can be used to identify novel ligands that bind perforin. Moreover, these molecules have superior physicochemical properties and solubility compared to previous generations of perforin ligands.
Topics: Perforin; Ligands; Killer Cells, Natural; Cell Death; Dapsone
PubMed: 37716187
DOI: 10.1016/j.ejmech.2023.115786 -
Journal of Drugs in Dermatology : JDD Nov 2023Management of hidradenitis suppurativa (HS) is challenging since no single treatment provides consistently effective results, leaving patients with frequent relapses....
BACKGROUND
Management of hidradenitis suppurativa (HS) is challenging since no single treatment provides consistently effective results, leaving patients with frequent relapses. Dapsone combines anti-microbial and anti-inflammatory properties that address aspects of HS pathogenesis. Few studies have evaluated the efficacy of oral dapsone on HS, especially in severe disease.
OBJECTIVE
This study aims to evaluate the clinical outcomes of patients with moderate-to-severe HS treated with dapsone.
METHODS
This retrospective chart review evaluated HS patients treated with oral dapsone over the past 10 years at one center. Treatment outcomes were classified based on Hurley staging, physician exam, and symptom progression. Adverse effects and concomitant treatment with dapsone were reviewed.
RESULTS
Nineteen (19) patients with moderate-to-severe (Hurley Stage II-III) HS treated with oral dapsone were identified. Within 1-3 months, on dosages of dapsone varying from 25-100 mg/day, 3 patients (15.8%) had a clinically significant improvement in symptoms, 10 patients (52.6%) had a slight improvement, and 6 patients (31.6%) had no change in disease state; no patients deteriorated. The majority who improved were also on other medications, most commonly adalimumab. 4 patients experienced adverse effects, with nausea being most common; otherwise, dapsone was well-tolerated.
CONCLUSIONS
Dapsone may have some efficacy for moderate-to-severe HS and seems well-tolerated. J Drugs Dermatol. 2023;22(11):e12-e16 doi:10.36849/JDD.4936e.
Topics: Humans; Hidradenitis Suppurativa; Retrospective Studies; Adalimumab; Drug-Related Side Effects and Adverse Reactions; Dapsone
PubMed: 37943259
DOI: 10.36849/JDD.4936 -
The Korean Journal of Pain Jul 2023There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through... (Review)
Review
There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through numerous mechanisms such as direct tissue damage and inflammation, the induction of excessive immunologic activity, and the development of peripheral or central sensitization. Treating infections might relieve pain by attenuating these processes, but a growing body of literature suggests that some antimicrobial therapies confer analgesic effects, including for nociceptive and neuropathic pain symptoms, and affective components of pain. The analgesic mechanisms of antimicrobials are indirect, but might be conceptualized into two broad categories: 1) the reduction of the infectious burden and associated pro-inflammatory processes; and 2) the inhibition of signaling processes (e.g., enzymatic and cytokine activity) necessary for nociception and maladaptive neuroplastic changes via off-target effects (unintended binding sites). For the former, there is evidence that symptoms of chronic low back pain (when associated with Modic type 1 changes), irritable bowel syndrome, inflammatory bowel disease, chronic pelvic pain, and functional dyspepsia might be improved after antibiotic treatment, though significant questions remain regarding specific regimens and dose, and which subpopulations are most likely to benefit. For the latter, there is evidence that several antimicrobial classes and medications exert analgesic effects independent of their reduction of infectious burden, and these include cephalosporins, ribavirin, chloroquine derivatives, rapalogues, minocycline, dapsone, and piscidin-1. This article aims to comprehensively review the existing literature for antimicrobial agents that have demonstrated analgesic efficacy in preclinical or clinical studies.
PubMed: 37394272
DOI: 10.3344/kjp.23129