Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

Ujiie, Hideyuki; Rosmarin, David; Schön, Michael P.; Ständer, Sonja; Boch, Katharina; Metz, Martin; Maurer, Marcus; Thaçi, Diamant; Schmidt, Enno; Cole, Connor; Amber, Kyle T.; Didona, Dario; Hertl, Michael; Recke, Andreas; Graßhoff, Hanna; Hackel, Alexander; Schumann, Anja; Riemekasten, Gabriela; Bieber, Katja; Sprow, Grant; Dan, Joshua; Zillikens, Detlef; Sezin, Tanya; Christiano, Angela M.; Wolk, Kerstin; Sabat, Robert; Kridin, Khalaf; Werth, Victoria P.; Ludwig, Ralf J.

doi:10.3389/fmed.2022.875492

Cited by 85 publications

(57 citation statements)

References 383 publications

(392 reference statements)

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“…Their adverse events and the underlying chronic inflammation may cause a significant comorbidity, especially metabolic and cardiovascular diseases. Early detection,individualization, and (in the future) potentially curative treatments will meet these medical needs in autoimmune diseases ( 12 ). Three articles of this Research Topic cover these aspects.…”

Section: Resolution Of Autoimmune Diseasementioning

confidence: 99%

“…Therefore, definite biomarkers that define the transition (i) from health to autoimmunity, (ii) from autoimmunity to autoimmune disease, and (iii) to chronicity or resolution of inflammation ( Figure 1 ) would allow to implement measures to slow or prevent disease progression. This would have a significant impact on affected individuals, as well as the healthcare system because the incidence of autoimmune and non-communicable inflammatory diseases is rising and there are still many unmet medical needs in the care of patients with these diagnoses ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Editorial: Autoimmune pre-disease

et al. 2023

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According to the revised Witebsky postulates, diseases are of an autoimmune nature if, (i) the clinical phenotype can be reproduced through the transfer of autoantibodies and/or lymphocytes; (ii) the disease can be reproduced in experimental animal models; (iii) autoreactive T cells or autoantibodies are identified; and/or (iv) distinctive clinical observations, such as an HLA association, are found (1). These postulates mostly still hold true despite they were made 3 decades ago. However, in psoriasis, lichen sclerosus and lichen planus, which are considered chronic, non-communicable inflammatory diseases, autoreactive T cells and/or autoantibodies that potentially contribute to disease pathogenesis are also detected (2-5). Thus, rather than a clear distinction between autoimmune and chronic non-communicable inflammatory diseases, categorization of a given distinct disease may be better placed in the continuum between the two. Hence, within this research topic, we cover both "classic" autoimmune diseases, such as systemic lupus erythematosus (SLE), as well as non-communicable, inflammatory diseases with detectable autoimmunity, e.g., psoriasis.Autoimmune diseases develop over a long time, which at least spans over several years. This is maybe best demonstrated by the presence of disease-specific autoantibodies years prior to diagnosis of the corresponding autoimmune disease (6-10). The presence of disease-specific autoantibodies, does not, however, reliably predict if clinical manifestation of the corresponding autoimmune disease will occur in the future. Therefore, definite biomarkers that define the transition (i) from health to autoimmunity, (ii) from autoimmunity to autoimmune disease, and (iii) to chronicity or resolution of inflammation (Figure 1) would allow to implement measures to slow or prevent disease progression. This would have a significant impact on affected individuals, as well as the healthcare system because the incidence of autoimmune and non-communicable inflammatory diseases is rising and there are still many unmet medical needs in the care of patients with these diagnoses (12, 13).

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Section: Resolution Of Autoimmune Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Editorial: Autoimmune pre-disease

et al. 2023

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“…Pathogenically, it is mediated by pathogenic autoantibodies that target desmoglein 1 and desmoglein 3 adhesion molecules of the epidermis that are responsible for the cohesion between keratinocytes in the skin and mucosa . Despite the substantial drop in the 1-year mortality rates of patients with pemphigus who receive proper treatment, they remain more susceptible to death compared with the general population …”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5] Despite the substantial drop in the 1-year mortality rates of patients with pemphigus who receive proper treatment, they remain more susceptible to death compared with the general population. [6][7][8][9] Systemic corticosteroids embodied the cornerstone of management of pemphigus for decades. All recent guidelines and consensus statements still define systemic corticosteroids as first-line therapy for pemphigus owing to their role in remission induction and consolidation.…”

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confidence: 99%

Association of Rituximab With Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients With Pemphigus

2023

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ImportanceThe association of different therapeutic approaches with long-term cardiovascular and metabolic outcomes in patients with pemphigus remains to be precisely evaluated.ObjectiveTo assess the risk of long-term cardiovascular and metabolic outcomes and all-cause mortality in patients with pemphigus managed by rituximab compared with those receiving treatment with first-line corticosteroid-sparing agents (azathioprine and mycophenolate mofetil [MMF]).Design, Setting, and ParticipantsA global population–based retrospective cohort study compared 961 patients with pemphigus that was managed with rituximab with those treated with azathioprine or MMF (n = 961) regarding the risk of several cardiovascular and metabolic outcomes. Propensity score matching was performed to optimize comparability. Patients were enrolled from the Global Collaborative Network of TriNetX platform.Main Outcomes and MeasuresRisk of myocardial infarction, stroke, peripheral vascular disease, pulmonary embolism, hypertension, hyperlipidemia, type 2 diabetes, obesity, osteoporosis, and avascular bone necrosis.ResultsOf 1602 participants, 855 (53.4%) were women and 747 (46.6%) were men; the mean (SD) age was 54.8 (16.6) years for those treated with rituximab and 54.4 (18.2) years for those treated with azathioprine or MMF. Compared with those treated by azathioprine/MMF, patients treated with rituximab experienced a lower risk of myocardial infarction (relative risk [RR], 0.45; 95% CI, 0.24-0.86; P = .01), stroke (RR, 0.42; 95% CI, 0.26-0.69; P &lt; .001), peripheral vascular disease (RR, 0.47; 95% CI, 0.28-0.79; P = .003), hypertension (RR, 0.48; 95% CI, 0.38-0.63; P &lt; .001), hyperlipidemia (RR, 0.45; 95% CI, 0.32-0.64; P &lt; .001), type 2 diabetes (RR, 0.63; 95% CI, 0.51-0.77; P &lt; .001), obesity (RR, 0.49; 95% CI, 0.34-0.72; P &lt; .001), and osteoporosis (RR, 0.46; 95% CI, 0.30-0.71; P &lt; .001). The all-cause mortality was comparable between patients in both groups (hazard ratio, 0.94; 95% CI, 0.62-1.43; log-rank P = .77).Conclusions and RelevanceThe results of this cohort study suggest that rituximab was associated with protection against long-term cardiovascular and metabolic outcomes compared with conventional immunosuppressants. This agent might be particularly preferred in individuals with preexisting cardiovascular and metabolic risk factors.

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“…Despite their low prevalence, AIBDs impose a significant medical burden, for both patients and the healthcare system. This is mainly due to the limited and partially insufficient treatment options, as well as a significant, often treatment-associated, (co)-morbidity [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study

et al. 2023

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Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2–5.5; p < 0.0001) in MMP to 28.7 (CI 3.9–211.3; p < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2–7.9; p < 0.0001) to 23.3 (CI 17.0–31.8; p < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.

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Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

Cited by 85 publications

References 383 publications

Editorial: Autoimmune pre-disease

Editorial: Autoimmune pre-disease

Association of Rituximab With Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients With Pemphigus

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study

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