Clinical manifestations of cutaneous lupus erythematosus

doi:10.1016/j.autrev.2005.01.003

Autoimmunity Reviews

Volume 4, Issue 5, June 2005, Pages 296-302

https://doi.org/10.1016/j.autrev.2005.01.003 Get rights and content

Abstract

The skin findings seen in lupus erythematosus can present with either lupus-specific or lupus-nonspecific findings, with lupus-specific skin disease showing findings histopathologically distinct for cutaneous lupus erythematosus. Lupus-specific skin diseases include chronic cutaneous, subacute cutaneous, and acute cutaneous lupus erythematosus. The types of skin lesions in each group are clinically distinct and recognizing the specific subsets helps in prognosticating the likelihood of underlying systemic lupus. A number of medications are associated with cutaneous lupus, in particular with subacute cutaneous lupus erythematosus. Lupus nonspecific skin lesions are not histopathologically distinct for cutaneous lupus and/or may be seen as a feature of another disease process. Nonspecific disease-related skin lesions are frequently seen in patients with SLE, usually in the active phase of the disease. The current ACR classification criteria for SLE include four somewhat overlapping dermatologic criteria, butterfly rash, discoid lupus, photosensitivity, and oral ulcers and thus patients can be classified as having SLE with only skin manifestations.

Section snippets

Epidemiology

SLE occurs in 17–48 persons/100,000 people. The cutaneous variants have been reported to be 2–3 fold more prevalent than SLE, and skin disease is the second most frequent clinical manifestation of SLE. Cutaneous LE is not infrequently associated with vocational disability [1].

Definition of the cutaneous manifestations of LE

The skin findings in cutaneous LE have been divided into two groups, LE-specific and LE-nonspecific skin disease [2], [3]. Biopsy of LE-specific skin lesions show LE-specific histology, and the diagnosis of LE can be confirmed regardless of whether sufficient ACR criteria are present for SLE. LE-nonspecific skin lesions are not histopathologically distinct for LE and/or may be seen as a feature of another disease process.

LE-specific skin lesions

Skin manifestations of LE are subsetted into chronic cutaneous LE, subacute cutaneous LE, and acute cutaneous LE [3]. A biopsy is recommended to confirm a clinical suspicion of cutaneous LE, since there are diseases that mimic the many variants of cutaneous LE. Since systemic evaluation and treatment are often indicated, it is important to confirm the clinical suspicion of cutaneous LE. Chronic cutaneous LE is the largest subset, and includes a number of entities that can be found as skin

Nonspecific LE-related skin lesions

Nonspecific disease-related skin lesions are frequently seen in patients with SLE, usually in the active phase of the disease [24]. Those with LE-nonspecific skin lesions have increased disease activity when compared to those with only LE-specific lesions and to those with both kinds of lesions [25]. The types of lesions, as discussed previously, have histology that is not distinct for LE and/or it may be seen as a feature of another disease process. The types of nonspecific LE-related skin

Conclusion

The diagnosis of the subtype of cutaneous LE can be helpful prognostically. It is still a challenge with lesions that are not LE-specific in histology but meet the criteria for the diagnosis of the entity. This would include subsets such as bullous SLE, Rowell's syndrome, and even LE tumidus. Lastly, there is a need for dermatologic involvement in future studies related to the criteria for classification of SLE.

Acknowledgments

This work is supported in part by grants from the Lupus Research Institute, a V.A. Merit Review Grant, and the National Institutes of Health (1K24AR002207).

Take-home messages

•
72–85% of SLE patients have skin involvement and 23–28% have skin involvement as the first manifestation of SLE
•
Skin lesions seen in LE are divided into lupus-specific and lupus-nonspecific
•
Patients with generalized discoid LE, SCLE, acute LE, or LE-nonspecific skin lesions are more likely to have systemic lupus than patients

References (33)

V.P. Werth et al.
Association of a promoter polymorphism of TNFalpha with subacute cutaneous lupus erythematosus and distinct photoregulation of transcription
J Invest Dermatol
(2000)
B. Tebbe et al.
Epidemiology and socioeconomic impact of skin disease in lupus erythematosus
Lupus
(1997)
J.N. Gilliam et al.
Distinctive cutaneous subsets in the spectrum of lupus erythematosus
J Am Acad Dermatol
(1982)
R.D. Sontheimer
The lexicon of cutaneous lupus erythematosus—a review and personal perspective on the nomenclature and classification of the cutaneous manifestations of lupus erythematosus
Lupus
(1997)
J.A. Yell et al.
Cutaneous manifestations of systemic lupus erythematosus
Br J Dermatol
(1996)
M. Viguier et al.
Clinical and histopathologic features and immunologic variables in patients with severe chilblains. A study of the relationship to lupus erythematosus
Medicine
(2005)
P.B. Martens et al.
Lupus panniculitis: clinical perspectives from a case series
J Rheumatol
(1999)
T. Watanabe et al.
Lupus erythematosus profundus: a cutaneous marker for a distinct clinical subset?
Br J Dermatol
(1996)
A. Kuhn et al.
Phototesting in lupus erythematosus tumidus—review of 60 patients
Photochem Photobiol
(2001)
A. Kuhn et al.
Upregulation of epidermal surface molecule expression in primary and ultraviolet-induced lesions of lupus erythematosus tumidus
Br J Dermatol
(2002)

M.R. Alexides-Armenakas et al.

Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis

Arthritis Rheum

(2003)

R.D. Sontheimer et al.

Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset

Arch Dermatol

(1979)

G.K. Perera et al.

Bullous subacute cutaneous lupus erythematosus

Clin Exp Dermatol

(2005)

L.A. Lee et al.

The autoantibody response to Ro/SSA in cutaneous lupus erythematosus

Arch Dermatol

(1994)

T.T. Provost et al.

Anti-Ro(SS-A) HLA-DR3-positive women: the interrelationship between some ANA negative, SS, SCLE, and NLE mothers and SS/LE overlap female patients

J Invest Dermatol

(1993)

R.D. Sontheimer et al.

Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus

Ann Intern Med

(1982)

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Comparison of patients with isolated cutaneous lupus erythematosus versus systemic lupus erythematosus with cutaneous lupus erythematosus as the sole clinical feature: A monocentric study of 149 patients
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Cutaneous lupus erythematosus (CLE) may present as an isolated entity or be classified as Systemic lupus erythematosus (SLE) by the presence of laboratory abnormalities, including cytopenia, low complement levels, and/or autoantibodies (CLE with laboratory SLE).
To compare isolated CLE and CLE with laboratory SLE and to validate an existing 3-item score with age < 25 years (1 point), phototypes V to VI (1 point), antinuclear antibodies ≥ 1:320 (5 points) to predict the risk of progression from CLE to severe SLE (sSLE).
Monocentric cohort study including consecutive patients with CLE. CLE with laboratory SLE was defined by 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE score of ≥10 points at baseline with CLE as the sole clinical feature.
Of the 149 patients with CLE, 20 had CLE with laboratory SLE. The median follow-up duration was 11.3 years (IQR: 5.1-20.5). Ten patients (7%) had sSLE developed. In survival analysis, the risk of progression to sSLE was higher among CLE with laboratory SLE (hazard ratio = 6.69; 95% CI: 1.93-23.14, P < .001) compared to isolated CLE. In both groups, none of the patients with a risk score ≤ 2 had sSLE developed.
Monocentric study with a limited number of patients.
CLE with laboratory patients with SLE have a higher risk of progression to sSLE than isolated CLE.
Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study
2023, eBioMedicine
Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted to be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings.
The Global Collaborative Network of TriNetX provides access to medical records of more than 120 million patients worldwide. We used TriNetX to elucidate the risk for cardiac and vascular diseases after diagnosis of CLE, and its subtypes chronic discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE). We included 30,315 CLE, 27,427 DLE, and 1613 SCLE patients. We performed propensity-matched cohort studies determining the risk to develop cardiac and vascular diseases (ICD10CM:I00-99) following diagnosis of CLE, DLE, or SCLE. Patients with systemic lupus erythematosus were excluded.
We document that CLE and its subtype DLE but less so SCLE are associated with a higher risk for various cardiac and vascular diseases. This included predominantly thromboembolic events such as pulmonary embolism, cerebral infarction, and acute myocardial infarction, but also peripheral vascular disease and pericarditis. For example, the hazard ratio of arterial embolism and thrombosis was 1.399 (confidence interval: 1.230–1.591, p < 0.0001) following CLE diagnosis. The study is limited by retrospective data collection and reliance on ICD10-disease classification.
CLE and its major subtype DLE are associated with an increased risk for the development of a wide range of cardiac and vascular diseases.
This research was funded by Deutsche Forschungsgemeinschaft (EXC 2167, CSSL/CS01-2022) and the Excellence-Chair Program of the State of Schleswig-Holstein.
Cutaneous manifestations in patients with systemic lupus erythematosus: Forms at the beginning of the disease and during follow-up. Retrospective analysis
2023, Reumatologia Clinica
Describir el compromiso cutáneo (CC) en pacientes con lupus eritematoso sistémico (LES) al inicio de la enfermedad y durante el seguimiento. Determinar factores asociados a dicho compromiso al comienzo de la enfermedad.
Estudio retrospectivo, observacional y descriptivo, de centro único, en pacientes con diagnóstico de LES (ACR 97 o SLICC 2012). Se utilizó la clasificación de Gilliam modificada para el CC. Se realizó estadística descriptiva y análisis bivariado y multivariado para evaluar los factores asociados al compromiso cutáneo.
Se incluyeron 149 pacientes (91,3% mujeres) con una mediana de edad al diagnóstico de 33 años. El CC al inicio de la enfermedad ocurrió en 125 pacientes (83,9%), seguido por compromiso articular en 120 (80,5%). Las lesiones no específicas fueron más frecuentes que las específicas: 92,8% versus 66,4%, respectivamente. En el análisis bivariado, la mayor demora al diagnóstico, la presencia de compromiso articular, la menor presencia de trombocitopenia y la mayor puntuación de SLEDAI-2K se asociaron con la presencia de CC al inicio de la enfermedad. En el análisis multivariado, la variable que se mantuvo asociada de manera independiente fue el compromiso articular (OR: 2,8; IC 95%: 1,1-7,5; p = 0,04). Durante el seguimiento, 4/24 pacientes que no habían presentado CC al diagnóstico y 51/125 pacientes que sí lo presentaron tuvieron al menos un nuevo episodio cutáneo (rango: 1-5 brotes).
Nuestro estudio demuestra la alta frecuencia de pacientes que presentan compromiso cutáneo en el LES, tanto en el diagnóstico como evolutivamente, y confirma los datos reportados previamente en cuanto a la existencia de un fenotipo cutáneo-articular.
To describe skin involvement (SI) in patients with systemic lupus erythematosus (SLE) at onset and during follow-up of the disease and to determine factors associated with SI at lupus diagnosis.
Retrospective, observational, and descriptive study, from a single centre in patients diagnosed with SLE (ACR 1982-97 or SLICC 2012 criteria). The modified Gilliam classification for SI was used. Descriptive statistics and bivariate and multivariate analysis were performed to evaluate the factors associated with SI at diagnosis of the disease.
A total of 149 patients were included, 91.3% women, with a median age at diagnosis of 33 years. SI at onset of the disease occurred in 125 patients (83.9%), followed by joint involvement in 120 cases (80.5%). Non-specific skin lesions were more frequent than specific lesions, 92.8% versus 66.4%, respectively. In the bivariate analysis, a longer delay to diagnosis, the presence of joint involvement, a lower presence of thrombocytopenia, and a higher SLEDAI-2K score were associated with the presence of SI at onset of the disease. In the multivariate analysis, the variable that remained independently associated was joint involvement (OR: 2.8: 95% CI: 1.1-7.5; P = .04). During follow-up, 4/24 patients who had not presented SI at diagnosis and 51/125 patients who had, had at least one new skin flare (range: 1-5 outbreaks).
Our study demonstrates the high frequency of skin involvement in SLE, both diagnostically and evolutionarily, and confirms previously reported data regarding the existence of a skin-articular phenotype.
Epidemiology of Cutaneous Lupus Erythematosus Among Adults Over Four Decades (1976-2018): A Lupus Midwest Network (LUMEN) Study
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To characterize the epidemiological trends and mortality of cutaneous lupus erythematosus (CLE) between 1976 and 2018 in Olmsted County, Minnesota.
In this retrospective population-based cohort study, all incident and prevalent CLE cases among adult residents in Olmsted County, Minnesota, between January 1, 1976, and December 31, 2018, were identified and categorized by subtype through medical record review using the resources of the Rochester Epidemiology Project.
The overall incidence rate of CLE between 1976 and 2018 was 3.9 (95% CI, 3.4 to 4.5) per 100,000. The incidence of CLE was relatively stable, with no major trend across sexes or age groups. The age- and sex-adjusted prevalence of CLE was 108.9 per 100,000 on January 1, 2015. Mortality in CLE patients was similar to that of the general population, with a standardized mortality ratio of 1.23 (95% CI, 0.88 to 1.66) with no observed trends in mortality over time.
In the past 4 decades, the incidence of CLE remained stable. Patients with CLE have mortality comparable to that of the general population.
Single-cell transcriptome reveals immunopathological cell composition of skin lesions in subacute cutaneous lupus erythematosus
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Subacute cutaneous lupus erythematosus (SCLE) is a clinical subtype of cutaneous lupus erythematosus with psoriatic-like or annular papules with scaly erythemas, the pathological mechanism of which is poorly understood. To investigate the immune pathogenesis of SCLE, we performed single-cell RNA sequencing (scRNA-seq) of SCLE skin lesions and integrated the scRNA-seq data from skin tissues of healthy controls (HCs). Our results identified expanded fibroblasts and keratinocytes subtypes, abnormally activated lymphocyte and inflammatory M1 macrophages in SCLE. In SCLE, stromal cells, such as keratinocytes and fibroblasts, showed enhanced chemotactic functions for recruiting immune cells. Importantly, interferon-related genes were identified as key intermediate genes in the potential trajectory of fibroblasts, keratinocytes, and B cells from HCs to SCLE. Our investigation provides a comprehensive description of cell composition in SCLE and highlights several important clues for understanding the pathogenesis of SCLE.
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Clinical manifestations of cutaneous lupus erythematosus

Abstract

Section snippets

Epidemiology

Definition of the cutaneous manifestations of LE

LE-specific skin lesions

Nonspecific LE-related skin lesions

Conclusion

Acknowledgments

J Invest Dermatol

Epidemiology and socioeconomic impact of skin disease in lupus erythematosus

Lupus

Distinctive cutaneous subsets in the spectrum of lupus erythematosus

J Am Acad Dermatol

The lexicon of cutaneous lupus erythematosus—a review and personal perspective on the nomenclature and classification of the cutaneous manifestations of lupus erythematosus

Lupus

Cutaneous manifestations of systemic lupus erythematosus

Br J Dermatol

Clinical and histopathologic features and immunologic variables in patients with severe chilblains. A study of the relationship to lupus erythematosus

Medicine

Lupus panniculitis: clinical perspectives from a case series

J Rheumatol

Lupus erythematosus profundus: a cutaneous marker for a distinct clinical subset?

Br J Dermatol

Phototesting in lupus erythematosus tumidus—review of 60 patients

Photochem Photobiol

Upregulation of epidermal surface molecule expression in primary and ultraviolet-induced lesions of lupus erythematosus tumidus

Br J Dermatol

Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis

Arthritis Rheum

Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset

Arch Dermatol

Bullous subacute cutaneous lupus erythematosus

Clin Exp Dermatol

The autoantibody response to Ro/SSA in cutaneous lupus erythematosus

Arch Dermatol

Anti-Ro(SS-A) HLA-DR3-positive women: the interrelationship between some ANA negative, SS, SCLE, and NLE mothers and SS/LE overlap female patients

J Invest Dermatol

Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus

Ann Intern Med