INTRODUCTION
Lupus erythematosus (LE) is a chronic autoimmune disease with multisystem organ involvement and is characterized by a broad spectrum of clinical, immunologic, and histologic manifestations. This condition most commonly affects young women between the ages of 20 and 40 years and results in an increased mortality risk due to a myriad of associated comorbidities.1 There are several different subtypes of this disease, one of which is cutaneous lupus erythematosus (CLE). CLE primarily presents in the skin and can occur as an isolated illness or in association with systemic lupus erythematosus (SLE). As its own entity, CLE has been found to occur 2 to 3 times more frequently than SLE.2,3 Moreover, up to 85% of individuals with SLE exhibit some form of cutaneous involvement throughout the course of their disease. Resultantly, individuals with chronic cutaneous findings affecting easily visible areas often face a significant psychological burden that further impacts their quality of life.
CLE can be further classified into acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and chronic cutaneous lupus erythematosus (CCLE), the latter of which discoid lupus erythematosus (DLE) is the most common.4,5 Each of these subgroups typically present with unique characteristics based on the extent of cutaneous involvement, lesion duration, and additional laboratory findings, as seen in Table 1.4 Global population studies estimate the prevalence of CLE at approximately 70 in 100 000.6,7 Furthermore, epidemiologic studies investigating LE and its subtypes have demonstrated an increased incidence of these diseases among Black patients as compared to their White counterparts.7
A variety of treatment modalities have been used in the management of CLE, including photoprotective strategies, sunscreen use, smoking cessation, topical corticosteroids, and calcineurin inhibitors, as well as systemic interventions with oral antimalarial agents and biologics.8 However, recent advances in immunomodulatory therapies offer potential new alternatives.8 Notably, a newly emerging drug class known as Janus kinase (JAK) inhibitors has been shown to be efficacious in managing symptoms associated with other known autoimmune conditions. As novel research further elucidates the intracellular signaling processes underlying the JAK/signal
CLE can be further classified into acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and chronic cutaneous lupus erythematosus (CCLE), the latter of which discoid lupus erythematosus (DLE) is the most common.4,5 Each of these subgroups typically present with unique characteristics based on the extent of cutaneous involvement, lesion duration, and additional laboratory findings, as seen in Table 1.4 Global population studies estimate the prevalence of CLE at approximately 70 in 100 000.6,7 Furthermore, epidemiologic studies investigating LE and its subtypes have demonstrated an increased incidence of these diseases among Black patients as compared to their White counterparts.7
A variety of treatment modalities have been used in the management of CLE, including photoprotective strategies, sunscreen use, smoking cessation, topical corticosteroids, and calcineurin inhibitors, as well as systemic interventions with oral antimalarial agents and biologics.8 However, recent advances in immunomodulatory therapies offer potential new alternatives.8 Notably, a newly emerging drug class known as Janus kinase (JAK) inhibitors has been shown to be efficacious in managing symptoms associated with other known autoimmune conditions. As novel research further elucidates the intracellular signaling processes underlying the JAK/signal
transducer and activator of transcription (STAT) pathway, improved targets within this drug class can be developed to address the underlying pathogenesis of inflammatory autoimmune diseases. This systematic review discusses the diagnosis and classification of CLE and its subtypes while also examining the potential role of JAK inhibitors in its treatment.
Classifying and Diagnosing CLE
Historically, quantifying CLE disease activity, progression, and outcome in clinical trials has been difficult due to the lack of appropriate measurement tools. In 2003, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed and validated by dermatologists and rheumatologists. The CLASI has 2 scores: disease activity and disease-induced damage. Disease activity measures erythema, scale/hypertrophy, mucous membrane involvement, hair loss in the past 30 days, and non-scarring alopecia for a maximum of 70 points. On the other hand, disease-induced damage measures the presence of dyspigmentation and scarring, including scarring alopecia, for a maximum of 80 points. If dyspigmentation has been present for more than 12 months, the score is doubled. Additionally, the CLASI weighs more exposed areas, such as the face, neck, and extensor surfaces of the arms, more heavily, correlating to the patient’s quality of life.9 Thus, higher numerical scores correlate to more severe disease. Furthermore, reductions in CLASI score reflect a reduction in disease activity.
Dyspigmentation disproportionally affects Black patients with CLE.10 Specifically, there is a 3- to 5-fold increase in the incidence of DLE in Black patients, and these patients more commonly display signs of disease damage such as ear and scalp hypopigmentation. 11 The mechanism of tissue damage, specifically dyspigmentation, is not well understood but is hypothesized to be secondary to inflammation at the basement membrane where the majority of melanocytes reside.12 Even when the disease process is well controlled, the outcome is a healed
Classifying and Diagnosing CLE
Historically, quantifying CLE disease activity, progression, and outcome in clinical trials has been difficult due to the lack of appropriate measurement tools. In 2003, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed and validated by dermatologists and rheumatologists. The CLASI has 2 scores: disease activity and disease-induced damage. Disease activity measures erythema, scale/hypertrophy, mucous membrane involvement, hair loss in the past 30 days, and non-scarring alopecia for a maximum of 70 points. On the other hand, disease-induced damage measures the presence of dyspigmentation and scarring, including scarring alopecia, for a maximum of 80 points. If dyspigmentation has been present for more than 12 months, the score is doubled. Additionally, the CLASI weighs more exposed areas, such as the face, neck, and extensor surfaces of the arms, more heavily, correlating to the patient’s quality of life.9 Thus, higher numerical scores correlate to more severe disease. Furthermore, reductions in CLASI score reflect a reduction in disease activity.
Dyspigmentation disproportionally affects Black patients with CLE.10 Specifically, there is a 3- to 5-fold increase in the incidence of DLE in Black patients, and these patients more commonly display signs of disease damage such as ear and scalp hypopigmentation. 11 The mechanism of tissue damage, specifically dyspigmentation, is not well understood but is hypothesized to be secondary to inflammation at the basement membrane where the majority of melanocytes reside.12 Even when the disease process is well controlled, the outcome is a healed
