What are the symptoms and treatment options for thymus gland disorders?

Management of Thymus Gland Disorders

Thymus transplantation is the definitive treatment for congenital athymia, with approximately 75% survival rate compared to poor outcomes with hematopoietic cell transplantation. 1

Symptoms of Thymus Gland Disorders

Thymus disorders present with varying symptoms depending on the specific condition:

Congenital Athymia

• Severe, recurrent infections (particularly viral, fungal, and opportunistic)
• Failure to thrive
• Features of immune dysregulation
• Omenn syndrome-like features (erythroderma, lymphadenopathy, hepatosplenomegaly)
• May have associated syndromic features (in DiGeorge syndrome or CHARGE syndrome) 1

Thymic Hypoplasia

• Milder T lymphocytopenia
• Less severe infections
• Improved T-cell counts with age due to homeostatic proliferation 1

Thymic Hyperplasia/Thymoma

• Often associated with autoimmune conditions like myasthenia gravis and ulcerative colitis
• Paraneoplastic syndromes (pure red cell aplasia, hypogammaglobulinemia) 2, 3
• Approximately 35% of thymomas are malignant (invasive or metastatic) 3

Thymic Involution (Age-related)

• Increased susceptibility to infections
• Higher risk of autoimmune disorders and cancers
• Restricted T-cell receptor repertoire 4

Diagnostic Approach

For Suspected Congenital Athymia:

1. Immunophenotyping:

   • Low total lymphocyte counts (may be normal due to B/NK cell expansion)
   • Negligible TRECs (T-cell receptor excision circles)
   • <5% of T lymphocytes with naive phenotype 1

2. Genetic Testing:

   • 22q11.2 deletion (DiGeorge syndrome)
   • CHD7 mutations (CHARGE syndrome)
   • Other genetic causes 1

3. Newborn Screening:

   • TREC-based screening programs can identify infants with thymic aplasia/hypoplasia 1

For Thymic Tumors:

• Imaging studies (CT, MRI)
• Pneumomediastinography for thymic hyperplasia/thymoma 2

Treatment Algorithm for Thymus Disorders

1. Congenital Athymia

• First-line treatment: Thymus transplantation 1

  • Available at Duke University Medical Center (US) and Great Ormond Street Hospital (UK)
  • Overall survival approximately 75%
  • Superior outcomes compared to hematopoietic cell transplantation

• Supportive care while awaiting transplantation:

  • Reverse isolation measures
  • Antimicrobial prophylaxis (trimethoprim-sulfamethoxazole, azole antifungals)
  • Immunoglobulin replacement therapy
  • Avoid live vaccines
  • Use only irradiated, CMV-negative blood products
  • Monitor for viral infections (CMV, EBV, adenovirus, HHV-6) 1

• For Omenn syndrome-like features:

  • Cyclosporine A (aim for trough levels 150-200 mg/L)
  • Topical corticosteroids for skin symptoms
  • Nutritional support
  • Consider systemic steroids in severe cases 1

2. Thymic Hypoplasia

• Less aggressive management than complete athymia
• Monitor T-cell counts and function
• Treat infections as they occur 1

3. Thymoma/Thymic Hyperplasia

• Thymectomy for thymomas and for associated autoimmune conditions
• Particularly effective for myasthenia gravis and ulcerative colitis 2
• Combined chemoimmunotherapy for malignant thymomas 5

4. Age-related Thymic Involution

• Strategies to mitigate thymic involution-associated complications
• Potential approaches to restore thymic function in elderly and immunocompromised individuals 4

Post-Transplantation Management for Congenital Athymia

• Continue immunoglobulin replacement therapy for 1-2 years until T-cell recovery
• Consider home therapy with subcutaneous immunoglobulin when available
• Begin immunizations 3 months after discontinuation of immunoglobulin therapy if IgG levels are normal
• Document protective antibody titers before administering live vaccines
• Monitor for autoimmune complications (particularly thyroid disease and cytopenias) 1

Common Pitfalls and Caveats

1. Delayed diagnosis: Early diagnosis and treatment of congenital athymia before infections develop leads to better outcomes 1

2. Misdiagnosis: Distinguishing between hematopoietic cell-intrinsic defects and thymic stromal defects is crucial as treatment approaches differ significantly 1

3. Overlooking comorbidities: Patients with athymia may need stabilization of cardiac, airway, or calcium abnormalities before thymus transplantation 1

4. Inadequate monitoring: Regular immunologic follow-up is essential to assess thymic output and T-cell function 1

5. Inappropriate HCT: Hematopoietic cell transplantation has poor outcomes in congenital athymia with survival rates below 50% and high risk of graft-versus-host disease 1