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International Journal of Molecular... Jun 2023Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph... (Review)
Review
Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called advanced pulmonary sarcoidosis, APS) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetic factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic characteristics and molecular pathways which are believed to be associated with the development of APS.
Topics: Humans; Pulmonary Fibrosis; Sarcoidosis; Sarcoidosis, Pulmonary; Lung; Granuloma
PubMed: 37445947
DOI: 10.3390/ijms241310767 -
Heart & Lung : the Journal of Critical... 2023Besides dyspnoea and cough, patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis may experience distressing non-respiratory symptoms, such as fatigue or...
INTRODUCTION
Besides dyspnoea and cough, patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis may experience distressing non-respiratory symptoms, such as fatigue or muscle weakness. However, whether and to what extent symptom burden differs between patients with IPF or sarcoidosis and individuals without respiratory disease remains currently unknown.
OBJECTIVES
To study the respiratory and non-respiratory burden of multiple symptoms in patients with IPF or sarcoidosis and to compare the symptom burden with individuals without impaired spirometric values, FVC and FEV1 (controls).
METHODS
Demographics and symptoms were assessed in 59 patients with IPF, 60 patients with sarcoidosis and 118 controls (age ≥18 years). Patients with either condition were matched to controls by sex and age. Severity of 14 symptoms was assessed using a Visual Analogue Scale.
RESULTS
44 patients with IPF (77.3% male; age 70.6±5.5 years) and 44 matched controls, and 45 patients with sarcoidosis (48.9% male; age 58.1±8.6 year) and 45 matched controls were analyzed. Patients with IPF scored higher on 11 symptoms compared to controls (p<0.05), with the largest differences for dyspnoea, cough, fatigue, muscle weakness and insomnia. Patients with sarcoidosis scored higher on all 14 symptoms (p<0.05), with the largest differences for dyspnoea, fatigue, cough, muscle weakness, insomnia, pain, itch, thirst, micturition (night, day).
CONCLUSIONS
Generally, respiratory and non-respiratory symptom burden is significantly higher in patients with IPF or sarcoidosis compared to controls. This emphasizes the importance of awareness for respiratory and non-respiratory symptom burden in IPF or sarcoidosis and the need for additional research to study the underlying mechanisms and subsequent interventions.
Topics: Humans; Male; Adolescent; Aged; Middle Aged; Female; Cough; Sleep Initiation and Maintenance Disorders; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Dyspnea; Fatigue; Muscle Weakness
PubMed: 37269615
DOI: 10.1016/j.hrtlng.2023.05.013 -
Clinical Pharmacology : Advances and... 2023Allopurinol is a commonly used medication that lowers uric acid production which is essential for gout treatment and prevention. Although many patients tolerate...
Allopurinol is a commonly used medication that lowers uric acid production which is essential for gout treatment and prevention. Although many patients tolerate allopurinol therapy without severe complications; Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening delayed hypersensitivity reactions that have been reported especially among Asian and African American patients. We describe a case of allopurinol-induced SJS in a 95-year-old Asian female. The patient started allopurinol 13 days prior to presenting to the emergency room (ER). On day 10 of therapy, the patient developed a diffuse erythematous desquamating rash which prompted her to visit the ER after 3 days from the rash onset. This case report describes a rare fatal hypersensitivity reaction that requires rapid identification and treatment in a multi-disciplinary setting.
PubMed: 37811521
DOI: 10.2147/CPAA.S427714 -
Journal of Family & Community Medicine 2023Despite the numerous reports of cutaneous manifestations associated with vaccines for coronavirus disease 2019 (COVID-19), the relationship between COVID-19 vaccines and... (Review)
Review
Despite the numerous reports of cutaneous manifestations associated with vaccines for coronavirus disease 2019 (COVID-19), the relationship between COVID-19 vaccines and cutaneous side effects remains unevaluated. In this review, we examine these manifestations and their management. Reported dermatoses included injection-site reaction (early and delayed), type I allergic reaction, morbilliform eruption, pityriasis rosea, Sweet syndrome, lichen planus, psoriasis, herpes zoster reactivation, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN). The most common COVID-19 vaccination-related cutaneous manifestations are delayed local reactions, approximately 66% of which are associated with the Moderna vaccine, and 33% with the Pfizer vaccine. Aside from mild injection-site reactions, severe reactions include anaphylaxis and TEN. Most reactions, except for Stevens-Johnson syndrome and anaphylaxis, though unpredictable and unpreventable are mild and can be treated symptomatically. Findings from this review should allow primary care physicians and dermatologists to reach faster diagnosis and initiate prompt intervention.
PubMed: 37675215
DOI: 10.4103/jfcm.jfcm_3_23 -
Circulation May 2024Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease,... (Review)
Review
Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.
Topics: Humans; Sarcoidosis; Cardiomyopathies; American Heart Association; United States; Adrenal Cortex Hormones; Disease Management
PubMed: 38634276
DOI: 10.1161/CIR.0000000000001240 -
European Annals of Allergy and Clinical... Dec 2023Metamizole, a non-steroidal anti-inflammatory drug from the pyrazolone group, is a frequent cause of immediate hypersensitivity reactions and, more rarely, of delayed...
Metamizole, a non-steroidal anti-inflammatory drug from the pyrazolone group, is a frequent cause of immediate hypersensitivity reactions and, more rarely, of delayed drug hypersensitivity reactions. Due to its favorable pharmacokinetic characteristics, metamizole is widely used in the postoperative period for pain control. Retrospective study of patients referred for allergological study between January 2012 and June2022 for postoperative hypersensitivity reactions. Clinical and diagnostic data were collected through review of patients' medical records. Twenty patients with postoperative hypersensitivity reactions were referred, of which 10 presented delayed reactions. We analyzed the results of skin prick, intradermal and patch tests performed with an intravenous metamizole solution as well as provocation tests performed with metamizole and acetylsalicylic acid. Cross-reactivity to non-steroidal anti-inflammatory drugs was excluded by confirmation of clinical tolerance to non-steroidal anti-inflammatory drugs or by acetylsalicylic acid provocation test. In 7 of the 10 patients a delayed reaction to metamizole was diagnosed. These reactions were characterized as maculopapular exanthema, occurring in multiple postoperative settings. Skin tests were negative, except in one patient with late mild erythema in the ipsilateral upper limb and no reaction at the site of intradermal injection. Delayed hypersensitivity was demonstrated by late positive metamizole provocation tests. This study demonstrated that for a correct diagnosis a high degree of suspicion about possible delayed hypersensitivity drug reactions to metamizole in the postoperative setting is needed. In the investigation, provocation test with metamizole was decisive for diagnostic confirmation.
PubMed: 38054601
DOI: 10.23822/EurAnnACI.1764-1489.317 -
Vaccine Jul 2023Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional...
Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.
Topics: Humans; Basophils; Excipients; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Hypersensitivity; Hypersensitivity, Delayed
PubMed: 37349223
DOI: 10.1016/j.vaccine.2023.06.039 -
Frontiers in Allergy 2023Approximately 10% of individuals report a suspected allergy to penicillin, but according to allergy work-ups, only 10%-15% of them are truly allergic. A clinical...
INTRODUCTION
Approximately 10% of individuals report a suspected allergy to penicillin, but according to allergy work-ups, only 10%-15% of them are truly allergic. A clinical decision score, the PEN-FAST, was developed and validated to identify adults with low-risk penicillin allergy.
OBJECTIVES
The objective of this study was to improve the performance of the PEN-FAST score, particularly for those with delayed hypersensitivity (HS), by improving the negative predictive value.
METHODS
STEP 1: Retrospective evaluation of the PEN-FAST score in patients with proven immediate and delayed penicillin allergy. STEP 2: Identification of additional criteria among Step 1 patients misclassified by PEN-FAST score. Development of the PEN-FAST+ score using multivariable logistic regression in a prospective cohort of patients with a suspicion of HS to penicillin. STEP 3: Comparison of diagnostic performances of PEN-FAST and PEN-FAST+ scores.
RESULTS
The PEN-FAST score showed limitations in predicting the relapse of immediate skin HS or delayed maculopapular exanthema, with 28.6% and 38.4% of patients misclassified, respectively. We identified two potential additional criteria: skin rash lasting more than 7 days and immediate reaction occurring in less than 1 h (generalized or localized on palmoplantar area or scalp itching/heat feeling). A total of 32/252 (12.7%) patients were confirmed to be allergic to penicillin. With PEN-FAST, 37% of patients ( = 10) with delayed allergic penicillin HS were misclassified. With PEN-FAST+, 3 patients with delayed HS confirmed by a ST (11.1%) were misclassified. The AUC was significantly higher for PEN-FAST+ than PEN-FAST (85% vs. 72%, = 0.03).
PubMed: 38026134
DOI: 10.3389/falgy.2023.1302567 -
Frontiers in Endocrinology 2023Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration... (Review)
Review
OBJECTIVE
Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D).
METHODS
We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic.
RESULTS
Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and insulin pump therapy. Multidisciplinary care involving pediatric endocrinology and allergy/immunology utilizing trials of many adjunct therapies yielded minimal improvement. Despite the use of various treatments, including antihistamines, topical therapies, immunosuppressant medications, desensitization trials, and intravenous immune globulin, cutaneous reactions, elevated hemoglobin A1c levels, and negative effects on quality of life remain persistent challenges. One patient became one of the youngest pancreas transplant recipients in the world at age 12 years due to uncontrollable symptoms and intolerable adverse effects of attempted therapies.
CONCLUSION
Although rare, insulin hypersensitivity reactions negatively affect glycemic control and quality of life. These cases demonstrate the varying severity and presentation of insulin hypersensitivity reactions along with the limited success of various treatment approaches. Given the life-sustaining nature of insulin therapy, further studies are needed to better understand the underlying pathophysiology of insulin hypersensitivity and to develop targeted treatment approaches.
Topics: Child; Humans; Adolescent; Diabetes Mellitus, Type 1; Quality of Life; Drug Hypersensitivity; Insulin; Urticaria
PubMed: 37929017
DOI: 10.3389/fendo.2023.1226231 -
The Journal of Allergy and Clinical... Dec 2023Elicitation of allergic contact dermatitis (ACD), an inflammatory type 4 hypersensitivity disease, induces skin infiltration by polyclonal effector CD8 αβ T cells and...
BACKGROUND
Elicitation of allergic contact dermatitis (ACD), an inflammatory type 4 hypersensitivity disease, induces skin infiltration by polyclonal effector CD8 αβ T cells and precursors of tissue-resident memory T (T) cells. Because T have long-term potential to contribute to body-surface immunoprotection and immunopathology, their local regulation needs a fuller understanding.
OBJECTIVE
We sought to investigate how T-cell maturation might be influenced by innate-like T cells pre-existing within many epithelia.
METHODS
This study examined CD8 T-cell maturation following hapten-induced ACD in wild-type mice and in strains harboring altered compartments of dendritic intraepidermal γδ T cells (DETCs), a prototypic tissue-intrinsic, innate-like T-cell compartment that reportedly regulates ACD, but by no elucidated mechanism.
RESULTS
In addition to eliciting CD8 T, ACD induced DETC activation and an intimate coregulatory association of the 2 cell types. This depended on DETC sensing IFN-γ produced by CD8 cells and involved programmed death-ligand 1 (PD-L1). Thus, in mice lacking DETC or lacking IFN-γ receptor solely on γδ cells, ACD-elicited CD8 T cells showed enhanced proliferative and effector potentials and reduced motility, collectively associated with exaggerated ACD pathology. Comparable dysregulation was elicited by PD-L1 blockade in vitro, and IFN-γ-regulated PD-L1 expression was a trait of human skin-homing and intraepithelial γδ T cells.
CONCLUSIONS
The size and quality of the tissue-infiltrating CD8 T-cell response during ACD can be profoundly regulated by local innate-like T cells responding to IFN-γ and involving PD-L1. Thus, interindividual and tissue-specific variations in tissue-intrinsic lymphocytes may influence responses to allergens and other challenges and may underpin inflammatory pathologies such as those repeatedly observed in γδ T-cell-deficient settings.
Topics: Animals; Humans; Mice; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Dermatitis, Allergic Contact; Interferon-gamma; Skin
PubMed: 37562754
DOI: 10.1016/j.jaci.2023.07.015