eMedicine Specialties > Dermatology > Allergy & Immunology

Severe Combined Immunodeficiency: Differential Diagnoses & Workup

Author: Henry K Wong, MD, PhD, Senior Professional Staff, Department of Dermatology, Henry Ford Hospital
Contributor Information and Disclosures

Updated: Dec 8, 2008

Differential Diagnoses

Cutaneous Manifestations of HIV Disease
Graft Versus Host Disease
Wiskott-Aldrich Syndrome

Other Problems to Be Considered

HIV and/or AIDS
Leiner disease
Letter Siwe histiocytosis
Primary immunodeficiency

Workup

Laboratory Studies

  • Blood count and/or blood smear: Children with severe combined immunodeficiency (SCID) have less than 3000/µL; however, a normal number of lymphocytes does not rule out SCID because the lymphocytes may be nonfunctional.
  • Immunoglobulin levels, especially the M component, can be low. However, soon after birth, immunoglobulin G (IgG) levels may be falsely elevated because of maternal IgG.
  • Other laboratory studies can be performed on the basis of clinical judgment, depending on the nature of the infection and the organ system involved. Specifically, assays that measure the ability of lymphocytes to respond to activating agents, such as pokeweed mitogen and phytohemagglutinin, are valuable.

Imaging Studies

  • Chest radiographs usually show an absent or small thymus shadow, and they can concomitantly display lung hyperinflation with an interstitial pneumonitis or pneumonia.
  • In ADA deficiency, chest radiographs show typical cupping and flaring of the costochondral junction.

Other Tests

  • Amniocentesis, chorionic villous biopsy sample, or cord blood can be used for prenatal diagnosis. Recently, 2 fetuses were successfully treated with gene therapy in utero with an injection of haploidentical CD34+ cells for the g chain deficiency.
  • Advanced assays of lymphocytes, if present, include measurements of the proliferative response of B cells and T cells to mitogens and lymphocyte subset analysis with flow cytometry. Analysis of specific genes associated with immunodeficiency may be helpful.
  • Test results may confirm the lack of a delay-type hypersensitivity cellular response to mumps, purified protein derivative (PPD), Candida species, and/or Trichophyton species.
  • The lack of an antibody response to tetanus toxoid may be observed.

Histologic Findings

  • The thymus is small with few thymocytes, and it lacks corticomedullary distinction and Hassall corpuscles. The epithelium is normal.
  • The spleen is depleted of lymphocytes.
  • The lymph nodes, tonsils, adenoids, and Peyer patches are underdeveloped or absent.
  • The epidermis can have foci of hyperkeratosis, with parakeratosis, or irregular acanthosis, with spongiosis and exocytosis. The papular dermis has edema and a diffuse perivascular infiltrate with some eosinophils.

More on Severe Combined Immunodeficiency

Overview: Severe Combined Immunodeficiency
Differential Diagnoses & Workup: Severe Combined Immunodeficiency
Treatment & Medication: Severe Combined Immunodeficiency
Follow-up: Severe Combined Immunodeficiency
References
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References

  1. Puck JM,. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. Oct 2007;120(4):760-8. [Medline].

  2. Ariga T. Gene therapy for primary immunodeficiency diseases: recent progress and misgivings. Curr Pharm Des. 2006;12(5):549-56. [Medline].

  3. Fischer A, Hacein-Bey S, Le Deist F, de Saint Basile G, Cavazzana-Calvo M. Gene therapy for human severe combined immunodeficiencies. Immunity. Jul 2001;15(1):1-4. [Medline].

  4. Friedrich W, Hönig M, Müller SM. Long-term follow-up in patients with severe combined immunodeficiency treated by bone marrow transplantation. Immunol Res. 2007;38(1-3):165-73. [Medline].

  5. Bonilla FA, Geha RS. 2. Update on primary immunodeficiency diseases. J Allergy Clin Immunol. Feb 2006;117(2 Suppl Mini-Primer):S435-41. [Medline].

  6. Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. Mar 1997;130(3):378-87. [Medline].

  7. Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. Feb 18 1999;340(7):508-16. [Medline].

  8. De Raeve L, Song M, Levy J, Mascart-Lemone F. Cutaneous lesions as a clue to severe combined immunodeficiency. Pediatr Dermatol. Mar 1992;9(1):49-51. [Medline].

  9. Fischer A. Primary immunodeficiency diseases: an experimental model for molecular medicine. Lancet. Jun 9 2001;357(9271):1863-9. [Medline].

  10. Gaspar HB, Gilmour KC, Jones AM. Severe combined immunodeficiency--molecular pathogenesis and diagnosis. Arch Dis Child. Feb 2001;84(2):169-73. [Medline].

  11. Gennery AR, Cant AJ. Diagnosis of severe combined immunodeficiency. J Clin Pathol. Mar 2001;54(3):191-5. [Medline].

  12. Grunebaum E, Mazzolari E, Porta F, Dallera D, Atkinson A, Reid B, et al. Bone marrow transplantation for severe combined immune deficiency. JAMA. Feb 1 2006;295(5):508-18. [Medline].

  13. Kovanen PE, Leonard WJ. Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. Immunol Rev. Dec 2004;202:67-83. [Medline].

  14. Postigo Llorente C, Ivars Amorós J, Ortiz de Frutos FJ, Regueiro JR, Llamas Martín R, Guerra Tapia A, et al. Cutaneous lesions in severe combined immunodeficiency: two case reports and a review of the literature. Pediatr Dermatol. Dec 1991;8(4):314-21. [Medline].

  15. Roifman CM, Zhang J, Chitayat D, Sharfe N. A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency. Blood. Oct 15 2000;96(8):2803-7. [Medline].

  16. Rosen FS. Severe combined immunodeficiency: a pediatric emergency. J Pediatr. Mar 1997;130(3):345-6. [Medline].

  17. Tsuji Y, Imai K, Kajiwara M, Aoki Y, Isoda T, Tomizawa D, et al. Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team. Bone Marrow Transplant. Mar 2006;37(5):469-77. [Medline].

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Further Reading

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Keywords

combined immunodeficiency, SCID, primary immunodeficiency, SCID with B cells, SCID without B cells

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Contributor Information and Disclosures

Author

Henry K Wong, MD, PhD, Senior Professional Staff, Department of Dermatology, Henry Ford Hospital
Henry K Wong, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Association of Immunologists, and Society for Investigative Dermatology
Disclosure: EISAI Consulting fee Speaking and teaching; Amgen Consulting fee Other; Abbott Labs Grant/research funds Other; Merck Honoraria Speaking and teaching

Medical Editor

James Fulton Jr, MD, PhD, Medical Director, Fulton Skin Institute
James Fulton Jr, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Cosmetic Surgery, American Academy of Dermatology, Phi Beta Kappa, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology
Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Honoraria Consulting; Centocor Honoraria Consulting; Genetech Honoraria Consulting; Celgene Honoraria Consulting

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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