What is the cause of Rowell syndrome, a condition characterized by the coexistence of lupus erythematosus (Systemic Lupus Erythematosus, SLE) and rheumatoid arthritis (RA) in a patient, particularly in women of childbearing age?

Rowell Syndrome: Etiology and Pathogenesis

Primary Cause

Rowell syndrome is an autoimmune disorder caused by the coexistence of lupus erythematosus (systemic or cutaneous) with erythema multiforme-like lesions, triggered by loss of immune tolerance and production of specific autoantibodies. 1, 2

Autoimmune Pathophysiology

The fundamental mechanism involves:

• Loss of immunological tolerance leading to pathogenic autoantibody production against nuclear antigens 3
• Immune complex deposition that activates complement, recruits inflammatory cells, and causes tissue damage 3
• Characteristic autoantibody profile including speckled pattern antinuclear antibodies (ANA), anti-Ro/SSA antibodies, anti-La/SSB antibodies, and rheumatoid factor 1, 2, 4

Triggering Factors

Multiple precipitants can unmask or exacerbate the syndrome:

• Medications are a major trigger, with documented cases following terbinafine, Helicobacter pylori eradication therapy, and other drugs 5
• Ultraviolet light exposure acts as an environmental trigger 1
• Infections, particularly bacterial infections, can precipitate disease onset 1
• COVID-19 vaccination has been identified as a recent triggering factor 1

Diagnostic Criteria

The syndrome requires specific immunological abnormalities for diagnosis:

Major Criteria (all three required):

• Presence of lupus erythematosus (acute, subacute, or systemic) 2, 4
• Erythema multiforme-like lesions without other precipitating factors 2, 4
• Speckled pattern of ANA staining 2, 4

Minor Criteria (at least one required):

• Chilblains 2, 4
• Positive anti-Ro/SSA or anti-La/SSB antibodies 2, 4
• Positive rheumatoid factor 2, 4

Genetic and Demographic Factors

• Female predominance during childbearing years, consistent with lupus erythematosus epidemiology 3
• Genetic susceptibility involving MHC polymorphisms that predispose to autoimmune disease 3
• Ethnic variations exist, with certain populations (Latin American, African descendants, Native Americans) experiencing more severe autoimmune manifestations 3

Distinction from Rhupus Syndrome

A critical caveat: The expanded question conflates Rowell syndrome with "Rhupus syndrome" (RA-lupus overlap), but these are distinct entities. Rowell syndrome specifically involves lupus with erythema multiforme-like lesions, not rheumatoid arthritis. 6 Rhupus syndrome refers to the coexistence of RA and SLE and represents a different diagnostic entity that may mimic difficult-to-treat RA 6.

Clinical Implications

• Rapid progression can occur, with cutaneous involvement spreading quickly from initial facial/truncal lesions to generalized distribution 2
• Systemic manifestations may include morning stiffness, peripheral arthritis, myalgia, and fatigue 5
• Rare complications such as macrophage activation syndrome have been reported, particularly in pediatric cases 7