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Internal Medicine

IPEX syndrome

IPEX (Immunodysregulation polyendocrinopathy enteropathy X-linked) syndrome is a rare disease linked to the dysfunction of the transcription factor FOXP3, widely considered to be the master regulator of the regulatory T cell lineage.

  • X-linked recessive (Xp11.23)

Pathophysiology

Genetic deficiency of FOXP3 (Expressed in regulatory T-cells)

Autoimmunity


Clinical features

Associated with diabetes in male infants.

  • Autoimmune enteropathy:
    • Diarrhoea
  • Autoimmune endocrinopathies:
    • Type I diabetes (71%)
    • Hypothyroidism (35%)
  • Autoimmune skin conditions:
    • Alopecia Universalis
    • Bullous pemphigoid
    • Psoriasiform or eczematous dermatitis
    • Nail dystrophy
m_dob30018f1
Clinical photographs of the patient’s skin and nails. A, Chronic scaly erythematous plaques were present on the flexural and extensor surfaces of the legs. B, Scaly, erythematous, eroded plaques on the penis and surrounding skin. C, Longitudinal ridging was present on numerous nails. D, Nonscarring alopecia of the scalp, eyebrows, and eyelashes. | DS, N., RP, P., SJ, P., & al, et. (2004). Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome. Archives of Dermatology, 140(4), 466–472. Retrieved from http://dx.doi.org/10.1001/archderm.140.4.466

Diagnosis

Histopathology

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Skin biopsy specimen of a new skin lesion on the left posterior thigh (hematoxylin-eosin, original magnification ×10). The biopsy findings are consistent with psoriasiform dermatitis. Sections showed irregular psoriasiform hyperplasia of the epidermis with overlying confluent parakeratosis. Exocytosis of mature lymphocytes into the epidermis with associated spongiosis was also noted. Immunocytochemical stains for CD4, CD5, and CD8 (not shown) were positive in approximately 99% of the cells, consistent with a predominantly T-cell infiltrate. Approximately 60% to 70% were positive for CD8, and 30% to 40% were positive for CD4. Periodic acid–Schiff stain results were negative for fungal organisms. | DS, N., RP, P., SJ, P., & al, et. (2004). Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome. Archives of Dermatology, 140(4), 466–472. Retrieved from http://dx.doi.org/10.1001/archderm.140.4.466

Differential diagnosis

gr2_lrg
Johnson, M. B., Hattersley, A. T., & Flanagan, S. E. (2016). Monogenic autoimmune diseases of the endocrine system. The Lancet Diabetes & Endocrinology, 4(10), 862–872. https://doi.org/10.1016/S2213-8587(16)30095-X

Management

  • Corticosteroids (first-line)
  • TPN (Total parenteral nutrition)
  • Immunosuppressives:
    • Cyclosporin A &Tacrolimus (FK506)
    • Sirolimus/Rapamycin (should FK506 prove non-effective)
  • Granulocyte colony-stimulating factor
  • Bone marrow transplant
  • Rituximab

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