Medicine

• Autoimmune diseases


  A diverse group of conditions characterized by an immune reaction against oneself
• More than 100 autoimmune diseases have been described, demonstrating a wide range of manifestations from organ-specific autoimmunity to organ-specific systemic manifestations to multiorgan systemic diseases
• Pathogenic mechanism in autoimmune disorders


  Breakdown in immune capacity, leading to autoreactive T lymphocytes and/or autoantibodies that give rise to autoimmunity
• The orofacial region, especially the oral mucosa and salivary glands, is affected by multiple autoimmune diseases, either directly as a manifestation of the clinical phenotype, or indirectly due to possible comorbidities or adverse effects of the drugs used for treatment
• Sjögren's syndrome


  An autoimmune disorder in which immune cells damage the salivary, tear, and other exocrine glands
• Forms of Sjögren's syndrome


  • Primary Sjögren's syndrome (dry eyes and mouth in the absence of connective tissue disease)
  • Secondary Sjögren's syndrome (dry eyes and mouth alongside other autoimmune diseases, usually affecting connective tissue)
• Systemic lupus erythematosus (SLE)


  A prototypic autoimmune disease with a broad spectrum of clinical manifestations and often unpredictable relapses
• The etiology and pathogenesis of SLE remain largely unknown, but it is recognized that genetic predisposition combined with environmental and possibly hormonal factors ultimately predisposes to disease
• Immune dysregulation in SLE results from the breakdown in tolerance to self-antigens, leading to excessive inflammation, autoantibody production, and destruction of end organs
• Immunological anomalies, particularly production of antinuclear antibodies (ANA) such as those against double-stranded (ds) DNA, are a hallmark of lupus
• Skin lesions in SLE


  • Butterfly rash on the face
  • Discoid lesions

  
• Females are affected 1.2-15 times more than males in SLE, and people of African descent have the highest prevalence while Caucasians have the lowest
• The peak ages of predominance for SLE are 45-69 for females and 40-89 for males
• Genetic susceptibility in SLE

  • High heritability (43.9%) and relative risk (5.87%) in first degree relatives of patients
• SLE can develop from a single-gene deficiency, but in most cases it results from a combination of multiple gene variant effects
• Hallmarks of lupus


  • Excessive inflammation
  • Deregulated IFN-I production
  • Defective clearance of apoptotic debris
  • T-cell/B-cell activation and autoantibody production with immune complex deposition
• Specific autoantibodies found to contribute to disease-related injury in SLE include anti-blood cell antibodies causing cytopenia, anti-dsDNA antibodies causing nephritis, and anti-phospholipid antibodies causing fetal resorption and other pathologic mechanisms
• Environmental factors, viral and other microbiome triggering, hormonal deregulations, and other environmental triggers such as ultraviolet radiation, tobacco consumption, and physiologic factors have been extensively hypothesized in the pathogenesis of SLE
• Nonspecific signs and symptoms in early SLE


  • Fatigue
  • Headache
  • Arthralgias
  • Lymph node enlargement
  • Fever
  • Significant weight loss
• Renal disease affects approximately 40-70% of SLE patients and is considered one of the major causes of morbidity and mortality
• Arthritis and arthralgias are a dominant feature of SLE, occurring in 65-70% of patients and tending to be migratory, polyarticular, and symmetric
• Cardiovascular manifestations in SLE typically include vasculitis and pericardial effusions, and can also involve myocarditis, endocardial involvement, atherosclerosis, valvular heart disease, and defective coagulation mechanisms
• Involvement of the central or peripheral nervous system in SLE presents diverse features and may be associated with poor prognosis
• Other manifestations of SLE


  • Pulmonary involvement (pleuritis, interstitial lung disease, pulmonary embolism)
  • Gastrointestinal disease (abdominal pain, nausea, vomiting, peritonitis, pancreatitis, enteritis, mesenteric vasculitis)
  • Genitourinary disorders (abortions associated with antiphospholipid syndrome)
  • Ocular manifestations (retinal involvement, keratoconjunctivitis)
• Mucocutaneous manifestations of SLE


  Most lupus patients will develop cutaneous and mucosal lesions during their disease, with tremendous variability in the type of skin involvement
• Cutaneous lupus erythema


  • Facial eruption ("butterfly rash") presenting as erythema in a malar distribution over the cheeks and nose
  • Discoid lesions that are more inflammatory and tend to scar
• Oral lesions in SLE occur in approximately 5-40% of patients, including nonspecific ulcerations and erythematous or discoid lesions mostly affecting the palatal mucosa, buccal mucosa, and gingiva
• The vermillion border of the lower lip can be characteristically involved (lupus cheilitis), and the temporomandibular joint (TMJ) can also be affected
• The oral manifestations of the cutaneous forms of lupus erythematosus closely mimic those of oral lichen planus, with characteristic central erythematous (erosive or atrophic) areas surrounded by white radiating striations
• A correlation between specific oral lesions and disease activity in cutaneous lupus erythematosus has been reported, as well as an association between gingivitis in cutaneous lupus and gingival telangiectasias in systemic lupus and systemic inflammation
• On rare occasions, squamous cell carcinoma may arise in discoid lesions affecting the lips or even intraoral sites in SLE patients
• Pathologic values in complete blood count (CBC) in SLE


  • Anemia
  • Leukopenia (lymphopenia and/or neutropenia)
  • Thrombocytopenia
• Erythrocyte sedimentation rate (ESR) is usually elevated along with normal C-reactive protein (CRP) in SLE, which is a characteristic feature
• Autoantibodies as biomarkers for SLE diagnosis


  • Antinuclear antibodies (ANAs) (positive in >95% of SLE patients)
  • Anti-double-stranded DNA (anti-dsDNA) antibodies (positive in ~50-70% of SLE patients)
  • Anti-Smith antigen (anti-Sm) antibodies (positive in ~30-40% of SLE patients)
  • Decreased complement markers (hypocomplementemia)
• Histopathology plays a crucial role in the diagnosis of SLE, including mucocutaneous involvement which should be investigated with histopathologic examination and immunofluorescence studies
• Cutaneous and oral mucosal lesions in SLE exhibit similar histopathologic features, including a superficial lymphocytic infiltrate, vacuolar degeneration of the basal cells, and thickening of the basement membrane
• Direct immunofluorescence can show subepithelial (or dermo-epidermal) immunoglobulin and complement deposition at the basement membrane zone in most lupus erythematosus lesions
• Management of SLE


  Challenging and depends on the extent of disease, the type of target organ(s), and the severity of manifestations, as well as possible morbidities
• Corticosteroids remain the main choice during management of SLE, but their long-term use can lead to common complications, so other immunosuppressive therapies are also used
• Lupus erythematosus lesions


  Subepithelial (or dermoepidermal) immunoglobulin and complement deposition (IgG, IgM, and C3) at the basement membrane zone can be found