What are the different types of lupus?

Types of Lupus

Yes, there are distinct types of lupus, primarily divided into systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), drug-induced lupus, and neonatal lupus, with CLE further subdivided into acute, subacute, chronic, and intermittent forms based on clinical presentation and duration of skin lesions. 1, 2

Major Categories of Lupus

Systemic Lupus Erythematosus (SLE)

• SLE is a multisystem autoimmune disease that can affect any organ or tissue in the body, characterized by clinical heterogeneity and the presence of diverse autoantibodies. 3
• The disease has an estimated prevalence of 20 to 150 cases per 100,000 population and is more common among women. 3
• SLE may be better conceptualized as a syndrome rather than a single disease—a collection of signs, symptoms, and phenomena that occur together and suggest a particular abnormality, with varied phenotypes potentially representing different diseases sharing similar clinical presentations. 4

Cutaneous Lupus Erythematosus (CLE)

CLE represents a spectrum of disease ranging from isolated skin involvement to manifestations occurring as part of SLE. 1, 5

The Four Main Subtypes of CLE:

1. Acute Cutaneous Lupus Erythematosus (ACLE)

• ACLE typically presents with the classic malar ("butterfly") rash and is most commonly associated with active systemic disease. 1, 2
• These lesions are usually transient and resolve without scarring. 2

2. Subacute Cutaneous Lupus Erythematosus (SCLE)

• SCLE manifests as photosensitive, annular or papulosquamous lesions, often in sun-exposed areas. 1, 2
• Drug-induced SCLE is a recognized entity, with many common medications including antihypertensives capable of triggering this subtype through mechanisms involving the interferon-I pathway. 6
• SCLE lesions typically heal without scarring but may leave dyspigmentation. 2

3. Chronic Cutaneous Lupus Erythematosus (CCLE)

• Discoid lupus erythematosus (DLE) is the most common form of CCLE, presenting as well-defined, disc-shaped plaques with adherent scale, follicular plugging, and central atrophy. 1, 2
• CCLE lesions are chronic and often result in permanent scarring, dyspigmentation, and alopecia when they affect the scalp. 2, 6
• Other CCLE variants include lupus profundus (lupus panniculitis), chilblain lupus, and tumid lupus. 2

4. Intermittent Cutaneous Lupus Erythematosus (ICLE)

• ICLE is characterized by recurrent episodes of skin lesions that resolve completely between flares. 2
• This category was added to the Düsseldorf Classification to account for patients with episodic cutaneous manifestations. 2

Classification Framework

The Düsseldorf Classification System

• The Düsseldorf Classification divides CLE into the four categories above based on clinical features, average duration of cutaneous lesions, histological changes, and laboratory abnormalities. 2
• These subtypes can have overlapping clinical features, and distinct subtypes may coexist within the same patient. 2, 6

Lupus Nephritis Classification

When lupus affects the kidneys, a separate classification system applies:

• The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification divides lupus nephritis into six histologic classes (I–VI), with the 2018 revision clarifying definitions to improve reproducibility. 7
• Class I represents minimal mesangial disease detectable only by immunofluorescence or electron microscopy. 7
• Class II involves mesangial proliferation with mesangial hypercellularity (≥4 mesangial cells per glomerular tuft). 3, 7
• Class III is focal lupus nephritis affecting <50% of glomeruli. 7
• Class IV is diffuse lupus nephritis affecting ≥50% of glomeruli and requires aggressive immunosuppression. 7
• Class V is membranous lupus nephritis with subepithelial immune deposits. 7
• Class VI represents advanced sclerosing disease with ≥90% glomerular sclerosis. 8

Diagnostic Considerations

Confirming CLE Diagnosis

• It is essential to confirm a CLE diagnosis histopathologically by biopsy because there are several differential diagnoses and CLE is a chronic disease requiring regular follow-up and sometimes systemic treatment. 1
• Direct immunofluorescence and photoprovocation testing may be applied to confirm the diagnosis in specific cases. 2

Distinguishing Between Types

• Differentiation between CLE subtypes is based on clinical features and average duration of cutaneous lesions, but also considers histological changes from skin biopsy specimens and laboratory abnormalities. 2
• A minimum of 10 glomeruli is required for adequate renal biopsy evaluation when lupus nephritis is suspected, with tissue processed for light microscopy, immunofluorescence, and electron microscopy. 7, 8

Clinical Implications

Risk of Systemic Progression

• Patients with isolated CLE, particularly DLE, have a lower risk of developing systemic disease compared to those with ACLE or SCLE. 1
• Regular monitoring for systemic involvement is essential, with heightened vigilance in Asian, African/Caribbean, Hispanic, and childhood-onset populations. 7

Common Pitfalls

• Do not rely solely on clinical appearance to classify lupus type—histopathology and laboratory testing are essential for accurate diagnosis and appropriate treatment planning. 1, 2
• Environmental triggers, particularly UV exposure and smoking, can induce and aggravate cutaneous lesions across all CLE subtypes. 6
• The clinical and serological heterogeneity of lupus raises the question of whether SLE represents a single disease with varied phenotypes or multiple diseases sharing similar presentations—this conceptual framework may allow for more targeted therapies and personalized medicine approaches in the future. 4