eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Leukocyte Adhesion Deficiency: Differential Diagnoses & Workup

Author: Stephen J Nervi, MD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey School of Medicine
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Monika I Sidor, MD, Staff Physician, Department of Surgery, University of Michigan at Ann Arbor
Contributor Information and Disclosures

Updated: Sep 9, 2009

Differential Diagnoses

Other Problems to Be Considered

These leukocyte adhesion deficiencies (LADs) are unlikely to be confused with hyperimmunoglobulin E syndrome or chronic granulomatous disease because the clinical features of infection resemble those manifested by patients with severe neutropenia despite marked neutrophilia. The neutrophils are mature, showing vacuoles and toxic granulations in the presence of infection, which is easily distinguished from myeloid leukemias.

A defect in a guanosine triphosphate (GTP)-binding protein, Rac2, which is integral to actin-associated neutrophil responses and to the generation of superoxide by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, leads to a clinical syndrome resembling Leukocyte adhesion deficiency with prolonged cord attachment, perirectal cellulitis, and omphalitis associated with marked leukocytosis and poor wound healing. However, integrin expression is intact. The mutation causes dominant-negative inhibition of Rac2-mediated neutrophil functions and low levels of Rac2 protein in the cytosol.

Healthy infants with delayed umbilical cord separation are not uncommon. The absence of leukocytosis distinguishes healthy infants from those with leukocyte adhesion deficiency.

Workup

Laboratory Studies

  • In leukocyte adhesion deficiency (LAD), the CBC count typically reveals leukocytosis (WBC count >20 X 109/L) in the absence of infection; leukocytosis dramatically increases with infection (WBC counts of 40-100 X 109/L are common).
  • Flow cytometry is used to assess the presence of the β2 integrins CD11a/CD18 (LFA-1 or aL/b2) on leukocytes, CD11b/CD18 (Mac-1 or aM/b2) on myeloid cells, and CD11c/CD18 (p150,95 or aX/b2) on myeloid cells.
  • In leukocyte adhesion deficiency II, the Bombay blood group phenotype is detected.
  • Preimplantation genetic diagnosis (PGD) of leukocyte adhesion deficiency I offers promise. The application of preimplantation genetic diagnosis has been developed to achieve a healthy pregnancy in one child.6 Thus, some evidence suggests that, for couples carrying mutated genes, traditional prenatal diagnosis and the decision of whether to terminate a pregnancy might not be acceptable because the application of PGD provides an alternative.

Imaging Studies

  • CT scanning and MRI are essential for diagnosis of abdominal infections in these patients because of the defective phagocytic mobilization to the site of infection. Plain radiographic findings are often misleading because of the absence of pus or lobar consolidation in pneumonia.
  • Bone scanning and gallium scanning may be useful modalities in localizing infection in selected patients. Because gallium relies on the presence of phagocytic cells, gallium scan findings are most likely to be informative when patients with leukocyte adhesion deficiency have residual expression of integrins or when granulocytes are transfused to patients with severe leukocyte adhesion deficiency (absence of CD18 expression).

Other Tests

  • In leukocyte adhesion deficiency I, assays of random migration, chemotaxis, phagocytosis, and killing by neutrophils invariably show deficits in these functions. Phagocytic and killing defects are caused by the impaired recognition of iC3b-opsonized organisms. Antibody-mediated cellular cytotoxicity is also impaired.
  • In leukocyte adhesion deficiency I, lymphocyte functions requiring LFA-1 (the CD2 pathway) are impaired; mitogen responses may be decreased. The relationship of in vitro lymphocyte defects to clinical infections is not understood. Although antibody responses to the T-dependent phiX174 bacteriophage were found to be impaired, immunoglobulin levels and specific antibody responses to vaccines are typically normal.
  • Leukocyte adhesion deficiency II is not associated with defects in lymphocyte or antibody function. The decrease in biochemical activity of guanosine 5'-diphosphate-D-mannose dehydratase (GMD) may be measured.

Procedures

  • Bronchoscopy may be required to identify the etiology of pulmonary infection.
  • Spinal taps have been carried out without complication.
  • Surgical procedures are fraught with difficulty caused by the extremely delayed healing. In the author's experience, wet-to-dry dressing changes are successful in promoting healing; granulocyte transfusions were not clinically successful.

Histologic Findings

  • In both leukocyte adhesion deficiency I and leukocyte adhesion deficiency II, localized infections lack neutrophilic infiltrates or pus formation; edema and necrosis are the prominent findings.

More on Leukocyte Adhesion Deficiency

Overview: Leukocyte Adhesion Deficiency
Differential Diagnoses & Workup: Leukocyte Adhesion Deficiency
Treatment & Medication: Leukocyte Adhesion Deficiency
Follow-up: Leukocyte Adhesion Deficiency
Multimedia: Leukocyte Adhesion Deficiency
References
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References

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Further Reading

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Keywords

leukocyte adhesion deficiency, leukocyte adhesion deficiency type 1, LAD 1, LAD 2, LAD I, LAD II, leukocytosis, localized bacterial infections, CDG-IIc, neutropenia, leukocytosis, congenital disorders of glycosylation, dysfunctional lipid-linked oligosaccharide precursor synthesis, dysfunctional trimming/processing of the protein-bound oligosaccharide, aseptic meningitis, crouplike syndromes, severe mental retardation and developmental delay, neurologic impairment, short stature, periodontitis, colitis, oral ulcerations, hematopoietic stem cell transplantation, delayed umbilical cord separation, omphalitis, perirectal cellulitis, labial cellulitis, otitis media, Staphylococcus species, Candida albicans, bacterial typhlitis, treatment, diagnosis

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Contributor Information and Disclosures

Author

Stephen J Nervi, MD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey School of Medicine
Stephen J Nervi, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Monika I Sidor, MD, Staff Physician, Department of Surgery, University of Michigan at Ann Arbor
Monika I Sidor, MD is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Terry Chin, MD, PhD, Associate Professor of Pediatrics, Pediatric Allergy/Immunology/Pulmonology, Department of Pediatrics, University of California Irvine School of Medicine; Associate Director, Miller Children's Hospital at Long Beach Memorial Medical Center
Terry Chin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American College of Chest Physicians, American Thoracic Society, California Thoracic Society, Clinical Immunology Society, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David J Valacer, MD, Consulting Staff, Hoffman La Roche Pharmaceuticals
David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.

CME Editor

David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville
David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology
Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD, Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School
Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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