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A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.Dermatology (Basel, Switzerland) 2024Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak.
OBJECTIVES
The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA).
METHODS
A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted.
RESULTS
A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI.
CONCLUSION
This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Topics: Humans; Clobetasol; Methotrexate; Network Meta-Analysis; Acetylcysteine; Bayes Theorem; Hydroxychloroquine; Lichen Planus; Cyclosporine; Alopecia; Chronic Disease
PubMed: 37852211
DOI: 10.1159/000534364 -
Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
Seminars in Arthritis and Rheumatism Dec 2023Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023.
RESULTS
Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk.
CONCLUSION
Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
Topics: Humans; Connective Tissue Diseases; Cyclophosphamide; Lung Diseases, Interstitial; Mycophenolic Acid; Glucocorticoids; Risk Factors; Diabetes Mellitus; Lymphopenia; Biological Products; Invasive Fungal Infections
PubMed: 37633041
DOI: 10.1016/j.semarthrit.2023.152257 -
Journal of Clinical Rheumatology :... Oct 2023To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK).
OBJECTIVE
To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK).
METHODS
A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members.
RESULTS
Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible.
CONCLUSION
The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.
Topics: Humans; United States; Takayasu Arteritis; Tumor Necrosis Factor Inhibitors; Rheumatology; Immunosuppressive Agents; Methotrexate
PubMed: 37553869
DOI: 10.1097/RHU.0000000000002004 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease...
BACKGROUND AND PURPOSE
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease of the central nervous system. The clinical features and prognosis of MOGAD adult cerebral cortical encephalitis (adult CCE) have not been fully elucidated. This study aims to further characterize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of CCE with anti-MOG antibody.
METHODS
We present two adult cases of CCE with anti-MOG antibody and summarize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of this phenotype as per a completed systematic review of the literature.
RESULTS
We found a total of 39 cases of MOGAD adult CCE (36% females; average age of onset of 29 years). Among them, 85% had seizure, 82% had headache, 64% had cortical symptoms, 64% had fever, 54% had changes of consciousness, and 38% had ocular symptoms. All cases demonstrated cerebral cortical T2 fluid-attenuated inversion recovery (FLAIR) lesions on MRI. Of the 25 patients (with seizure or not) who had EEG reports, 76% of patients showed abnormal EEG. Cerebrospinal fluid (CSF) white blood cell count of 90% of patients and CSF total protein of 67% of patients were elevated. In 16 patients with available CSF cytology data, 11 (69%) had abnormal cytology findings with monocytic predominance. In the 15 cases for which MOG antibody IgG was tested in both serum and CSF, 14 (93%) demonstrated a higher positive MOG IgG titer in serum than CSF. The majority of patients were treated with immunosuppressive therapy (97% corticosteroids, 15% mycophenolate mofetil, 13% IVIg, 5% azathioprine, and 5% other). The majority of patients had a favorable prognosis after treatment, as exemplified by improved clinical symptoms and imaging. Two patients relapsed.
CONCLUSIONS
The clinical presentation and prognosis of adult CCE remain less understood in comparison to more common MOGAD phenotypes. It is important to consider MOGAD as an underlying etiology for adult CCE, as early detection and immunotherapy may improve outcomes.
Topics: Female; Male; Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Encephalitis; Seizures; Immunoglobulin G; Oligodendroglia
PubMed: 37520572
DOI: 10.3389/fimmu.2023.1203615 -
Vaccines Jun 2023Solid organ transplant (SOT) recipients are at increased risk of COVID-19 infection because of their suppressed immunity. The available data show that COVID-19 vaccines... (Review)
Review
Solid organ transplant (SOT) recipients are at increased risk of COVID-19 infection because of their suppressed immunity. The available data show that COVID-19 vaccines are less effective in SOT recipients. We aimed to assess the cellular and humoral immunogenicity with an increasing the number of doses of COVID-19 vaccines in SOT recipients and to identify factors affecting vaccine response in this population. A systematic review and meta-analysis were conducted to identify ongoing and completed studies of humoral and cellular immunity following COVID-19 vaccines in SOT recipients. The search retrieved 278 results with 45 duplicates, and 43 records did not match the inclusion criteria. After title and abstract screening, we retained 189 records, and 135 records were excluded. The reasons for exclusion involved studies with immunocompromised patients (non-transplant recipients), dialysis patients, and individuals who had already recovered from SARS-CoV-2 infection. After full-text reading, 55 observational studies and randomized clinical trials (RCTs) were included. The proportion of responders appeared higher after the third, fourth, and fifth doses. The risk factors for non-response included older age and the use of mycophenolate mofetil, corticosteroids, and other immunosuppressants. This systematic review and meta-analysis demonstrates the immunogenicity following different doses of COVID-19 vaccines among SOT patients. Due to the low immunogenicity of vaccines, additional strategies to improve vaccine response may be necessary.
PubMed: 37514982
DOI: 10.3390/vaccines11071166 -
Rheumatology International Jul 2023Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a...
Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4 years and NMOSD onset was 43.2 ± 19.8 years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.
PubMed: 37500817
DOI: 10.1007/s00296-023-05397-0 -
Lupus Sep 2023Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those...
BACKGROUND
Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those of neuropsychiatric manifestations of SLE. Pathogenic anti-aquaporin-4 (AQP4) antibodies, commonly found in NMOSD, are responsible for the neuroinflammatory response and secondary demyelinating lesions. These anti-AQP4 antibodies can be the drivers of neuroinflammatory process in SLE patients, which is distinct from the immunopathogenesis seen in traditional neuropsychiatric SLE. The clinical course is often a relapsing one and is managed differently. In this review, we describe and outline the clinical course and outcomes of AQP4+ NMOSD/SLE overlap cases.
METHODS
To investigate the co-existence of SLE with AQP4+NMOSD, we conducted a systematic review of individual patient data from case reports and case series reported in major databases. The study extracted clinic-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for AQP4 or NMO in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both NMOSD and SLE.
RESULTS
In this overlap between SLE and AQP4+NMOSD, a high female preponderance was observed, with 42 out of 46 patients (91.3%) being female. Nearly half of the NMOSD cases (47.8%) had onset after lupus, with a median of 5 years between the two diagnoses. Hematological manifestations were seen in the majority of patients (63%), as well as longitudinally extensive transverse myelitis (87%), and brainstem involvement on imaging (29.6%). Cerebrospinal fluid analysis showed a dominantly lymphocytic pleocytosis, with oligoclonal bands being reported scarcely. Although cyclophosphamide was the most common steroid sparing agent used for maintenance, robust evidence for both efficacy and safety in AQP4+NMOSD is available for mycophenolate mofetil, azathioprine, and rituximab. The majority of reported cases showed a relapsing course, while one patient had a monophasic course.
CONCLUSION
AQP4+NMOSD in SLE patients is a relapsing and neurologically disabling disorder that can mimic neuropsychiatric manifestations, frequently occurs after the onset of lupus or may predate, responds to immunosuppressants, and necessitates indefinite treatment.
Topics: Humans; Female; Male; Neuromyelitis Optica; Lupus Erythematosus, Systemic; Neoplasm Recurrence, Local; Aquaporin 4; Syndrome; Disease Progression; Autoantibodies
PubMed: 37487596
DOI: 10.1177/09612033231191180 -
Vaccines Jun 2023The pediatric population is at a lower risk of severe SARS-CoV-2 infection compared to adults. Nevertheless, immunosuppression in pediatric and adolescent kidney... (Review)
Review
The pediatric population is at a lower risk of severe SARS-CoV-2 infection compared to adults. Nevertheless, immunosuppression in pediatric and adolescent kidney transplant recipients (KTRs) increases their hazard compared to the general population. This systematic review evaluates the efficacy of SARS-CoV-2 vaccines and determines the risk factors of no seroconversion in this population. PubMed-MEDLINE databases were searched for cohort studies. A meta-analysis was performed using fixed and random effect models. In total, seven studies including 254 patients were further analyzed. The random effect model demonstrated a 63% seroconversion rate (95% CI 0.5, 0.76) following a two-dose schedule, which increased to 85% (95% CI 0.76, 0.93) after the third dose administration. Seropositivity was lower in patients under mycophenolate mofetil compared to azathioprine (OR 0.09, 95% CI 0.02, 0.43). Rituximab administration decreased the seroconversion rate (OR 0.12, 95% CI 0.03, 0.43). The glomerular filtration rate (GFR) was 9.25 mL/min/1.73 m lower (95% CI 16.37, 2.13) in patients with no seroconversion. The seroconversion rate was lower in vaccinated compared to infected patients (OR 0.13, 95% CI 0.02, 0.72). In conclusion, vaccination against SARS-CoV-2 in pediatric and adolescent KTRs elicits a humoral response, and a third dose is advised. Previous rituximab administration, antimetabolite therapy with mycophenolate mofetil and lower GFR reduce the likelihood for seroconversion.
PubMed: 37376469
DOI: 10.3390/vaccines11061080 -
Vaccine Jun 2023Patients with autoimmune rheumatic diseases (ARD) are at a potentially higher risk for COVID-19 infection complications. Given their inherent altered immune system and... (Review)
Review
BACKGROUND
Patients with autoimmune rheumatic diseases (ARD) are at a potentially higher risk for COVID-19 infection complications. Given their inherent altered immune system and the use of immunomodulatory medications, vaccine immunogenicity could be unpredictable with a suboptimal or even an exaggerated immunological response. The aim of this study is to provide real-time data on the emerging evidence of COVID-19 vaccines' efficacy and safety in patients with ARDs.
METHODS
We performed a literature search of the PubMed, EMBASE, and OVID databases up to 11-13 April 2022 on the efficacy and safety of both types of the mRNA-vaccines and the AstraZeneca COVID-19 vaccines in patients with ARD. The risk of bias in the retrieved studies was evaluated using the Quality in Prognostic Studies tool. Also, current clinical practice guidelines from multiple international professional societies were reviewed.
RESULTS
We identified 60 prognostic studies, 69 case reports and case series, and eight international clinical practice guidelines. Our results demonstrated that most patients with ARDs were able to mount humoral and/or cellular responses after two doses of COVID-19 vaccine although this response was suboptimal in patients receiving certain disease-modifying medications including rituximab, methotrexate, mycophenolate mofetil, daily glucocorticoids >10 mg, abatacept, as well as in older individuals, and those with comorbid interstitial lung diseases. Safety reports on COVID-19 vaccines in patients with ARDs were largely reassuring with mostly self-limiting adverse events and very minimal post-vaccination disease flares.
CONCLUSION
Both types of the mRNA-vaccines and the AstraZeneca COVID-19 vaccines are highly effective and safe in patients with ARD. However, due to their suboptimal response in some patients, alternative mitigation strategies such as booster vaccines and shielding practices should also be followed. Management of immunomodulatory treatment regimens during the peri vaccination period should be individualized through shared decision making with patients and their attending rheumatologists.
Topics: Humans; Aged; COVID-19 Vaccines; RNA, Messenger; COVID-19; ChAdOx1 nCoV-19; Autoimmune Diseases; Rheumatic Diseases
PubMed: 37244811
DOI: 10.1016/j.vaccine.2023.05.048