An Update on the Pathogenesis of Cutaneous Lupus Erythematosus and Its Role in Clinical Practice

Patel, Jay; Borucki, Robert; Werth, Victoria P.

doi:10.1007/s11926-020-00946-z

Cited by 14 publications

(11 citation statements)

References 142 publications

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“…Various external factors including drugs and vaccines are known to induce disease flares in CLE, especially in SCLE. 2 To our knowledge, three similar cases of post-vaccination CLE have been reported. [3][4][5] All were classified clinically as SCLE, and all occurred within 10 days after application of the first vaccination dose and rapidly responded to treatment with systemic corticosteroids (Table 1).…”

mentioning

confidence: 93%

“…6 The type 1 IFN pathway is also a major component of CLE pathogenesis, and correlates with disease activity. 2 Interestingly, among ANA-positive clinically asymptomatic patients, anti-Ro/SSA and/or anti-La/ SSB antibodies were associated with an elevated IFN signature and the lupus-risk variant IRF5. 6 These findings might explain why all of the reported post-vaccination lupus cases had Ro/SSA-positive SCLE (Table 1).…”

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confidence: 99%

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Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA‐based or adenoviral vector‐based SARS‐CoV‐2 vaccination

Kreuter

Licciardi-Fernandez

Burmann

et al. 2021

Clin Experimental Derm

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Correspondence urticarial and morbilliform eruptions. Less frequently seen reactions included chilblains, cosmetic filler reactions, herpes zoster or herpes simplex flares, and pityriasis rosea-like reactions. Only two patients had cutaneous vasculitis. Lupus-like skin lesions or lupus deterioration were not reported. 7 Strong agreement exists that all patients with autoimmune rheumatic diseases should be vaccinated against COVID-19. However, SARS-CoV-2 vaccination should be considered as a potential trigger of disease flares, especially in individuals with certain ANA constellations (e.g. anti-Ro/SSA and anti-La/SSB antibodies) predisposing for CLE.

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confidence: 93%

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confidence: 99%

Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA‐based or adenoviral vector‐based SARS‐CoV‐2 vaccination

Kreuter

Licciardi-Fernandez

Burmann

et al. 2021

Clin Experimental Derm

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“…LE may have broad clinical manifestations, include cutaneous lesions. Cutaneous lesions can be observed in absence of systemic signs of the diseases, or in the presence of systemic disease, namely systemic lupus erythematosus (SLE) [1]. The cutaneous forms of LE can be classified as acute cutaneous LE, subacute cutaneous LE, and discoid lupus erythematosus (DLE).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike patients with SLE, those affected by DLE do not exhibit high titers of anti-Ro antibodies which might indicate the absence of a systemic autoreactivity in DLE. Nonetheless, it is known that patients with DLE are at a risk to develop SLE [1,2], and have a higher incidence of developing squamous cell carcinoma in the scarred areas [3]. Drug treatments of DLE include topical agents (steroids and calcineurin inhibitors) and systemic agents, such as hydroxychloroquine, retinoids, and azathioprine [3].…”

Section: Introductionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

et al. 2021

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Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.

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“…Photosensitivity, an abnormal sensitivity of the skin to ultraviolet radiation (UVR), is considered to be a major contributor to CLE inflammatory lesion development and can also trigger flares of systemic disease in SLE (Patel et al, 2020;Sim et al, 2021). Recent evidence has pointed to a role for IFN-I in photosensitivity.…”

Section: Introductionmentioning

confidence: 99%

The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus

Veiga

Schwartz

et al. 2021

Preprint

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Type I IFN (IFN-I) mediates autoimmune and inflammatory conditions, and better understanding IFN-I-driven pathogenesis could expand therapeutic possibilities. Lupus is an autoimmune disease characterized by photosensitivity, inflammatory skin lesions, and systemic organ damage. Patients have an IFN-I signature in blood and tissues and anifrolumab (anti-IFNAR1), developed for lupus and recently FDA-approved, underscores the importance of IFN-I in pathogenesis. Anifrolumab is especially efficacious for cutaneous disease, but mechanisms are poorly understood. Langerhans cells (LCs) normally limit UVR-induced skin injury via ADAM17, a metalloprotease that clips from the cell membrane and activates skin-protective EGFR ligands. Downregulation of LC ADAM17 mRNA and activity in lupus models contributes to photosensitivity, and here we link IFN-I pathogenesis with LC dysfunction. We show that murine model and human lupus non-lesional skin have IFN-I signatures and that IFN-I reduces ADAM17 sheddase activity in LCs. Furthermore, anti-IFNAR1 in multiple murine lupus models restores LC ADAM17 function and reduces photosensitivity in an EGFR and LC ADAM17-dependent manner. These results suggest that IFN-I contributes to photosensitivity in lupus by downregulating LC ADAM17 function, providing mechanisms for IFN-I pathogenesis and anifrolumab efficacy and highlighting the importance of LCs as a potential therapeutic target.

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An Update on the Pathogenesis of Cutaneous Lupus Erythematosus and Its Role in Clinical Practice

Cited by 14 publications

References 142 publications

Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA‐based or adenoviral vector‐based SARS‐CoV‐2 vaccination

Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA‐based or adenoviral vector‐based SARS‐CoV‐2 vaccination

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus

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