What are the differences between Sjogren syndrome and Sjogren-Larsson syndrome?

Differences Between Sjögren's Syndrome and Sjögren-Larsson Syndrome

Sjögren's syndrome and Sjögren-Larsson syndrome are completely unrelated disorders with distinct pathophysiology, clinical manifestations, and management approaches, despite the similarity in names.

Sjögren's Syndrome

Sjögren's syndrome is an autoimmune disorder characterized by:

• Pathophysiology: Autoimmune disease with lymphocytic infiltration of exocrine glands
• Epidemiology:
  • Prevalence of approximately 0.4% of the population
  • Female-to-male ratio of 20:1
  • Annual incidence of 3.9-5.3 per 100,000 1

Key Clinical Features:

• Glandular manifestations:

  • Dry eyes (keratoconjunctivitis sicca)
  • Dry mouth (xerostomia)
  • Swollen salivary glands

• Extraglandular manifestations:

  • Fatigue
  • Joint and muscle pain
  • Raynaud's phenomenon
  • Skin dryness
  • Vaginal dryness 1

Diagnostic Criteria:

According to the American College of Rheumatology and European League Against Rheumatism, diagnosis requires a score of ≥4 based on:

• Anti-SSA/Ro antibody positivity (3 points)
• Focal lymphocytic sialadenitis (3 points)
• Abnormal ocular staining score (1 point)
• Schirmer test ≤5 mm/5 minutes (1 point)
• Unstimulated salivary flow rate ≤0.1 ml/minute (1 point) 1

Management:

• Artificial tears and lubricants for dry eyes
• Saliva substitutes and oral secretagogues (pilocarpine, cevimeline) for dry mouth
• Hydroxychloroquine for fatigue and arthralgia
• Immunomodulatory therapy for systemic manifestations 1

Sjögren-Larsson Syndrome

Sjögren-Larsson syndrome is a rare genetic disorder characterized by:

• Pathophysiology: Autosomal recessive inborn error of lipid metabolism caused by mutations in the ALDH3A2 gene, resulting in deficiency of fatty aldehyde dehydrogenase (FALDH) 2, 3

• Epidemiology:

  • Rare disorder with high prevalence in Sweden (where it was first described)
  • Occurs worldwide with no gender predilection 3

Key Clinical Features:

• Classical triad:

  • Congenital ichthyosis (dry, scaly skin)
  • Spastic diplegia or tetraplegia
  • Intellectual disability 3, 4

• Other features:

  • "Glistening white dots" in the retina (pathognomonic)
  • Preterm birth is common
  • Leukoencephalopathy on brain MRI
  • Characteristic abnormal lipid peak on MR spectroscopy 3

Diagnostic Criteria:

• Clinical suspicion based on the classical triad
• Demonstration of FALDH enzyme deficiency
• Genetic testing showing biallelic mutations in ALDH3A2 gene 3, 4

Management:

• Primarily symptomatic:
  • Topical emollients and frequent bathing for ichthyosis
  • Supportive care for neurological manifestations
  • Potential experimental therapies include aldehyde scavenging drugs, ALDH-specific activators, and gene therapy 2, 5

Key Differences

Feature	Sjögren's Syndrome	Sjögren-Larsson Syndrome
Etiology	Autoimmune	Genetic (ALDH3A2 mutations)
Inheritance	Not inherited	Autosomal recessive
Age of onset	Adult (typically)	Congenital/infancy
Key manifestations	Dry eyes, dry mouth	Ichthyosis, spasticity, intellectual disability
Laboratory findings	Anti-SSA/Ro antibodies	FALDH enzyme deficiency
Treatment approach	Symptom management, immunomodulation	Symptomatic, experimental therapies

Clinical Pearls

• Despite the similar names, these conditions have no pathophysiological relationship
• Sjögren's syndrome is relatively common, while Sjögren-Larsson syndrome is extremely rare
• Sjögren's syndrome typically presents in adulthood, while Sjögren-Larsson syndrome manifests from birth
• Skin involvement in Sjögren's syndrome is mild dryness, while in Sjögren-Larsson syndrome it is severe congenital ichthyosis
• Neurological involvement in Sjögren's syndrome is peripheral neuropathy, while in Sjögren-Larsson syndrome it is central with spasticity and intellectual disability