A 3-year-old girl is brought to the emergency department due to severe oral pain. The pain began 2 weeks ago with discomfort while chewing and has progressively worsened; she now refuses any oral intake. The patient had a similar episode of oral pain last year. Medical history includes 2 sinus infections and numerous episodes of nonpurulent cellulitis. Skin cultures from previous infections isolated Staphylococcus aureus and Streptococcus pyogenes. Physical examination shows periodontal inflammation with ulceration and necrosis. The results of a complete blood count are as follows:
| Hemoglobin | 11.8 g/dL |
| Hematocrit | 36% |
| Platelets | 240,000/mm3 |
| Leukocytes | 55,000/mm3 |
| Neutrophils | 90% |
| Lymphocytes | 8% |
| Monocytes | 2% |
Which of the following abnormalities is most likely present in this patient?
Leukocyte adhesion deficiency | |
Pathophysiology |
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Clinical features |
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Laboratory findings |
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This patient's recurrent bacterial infections, severe periodontitis, and marked leukocytosis are consistent with leukocyte adhesion deficiency (LAD). LAD is caused by defective integrins on the leukocyte surface, which normally allow neutrophil adhesion to the vascular endothelium, exit from the vasculature, and migration to areas of infection or inflammation.
Lack of neutrophil migration in LAD classically presents in the neonatal period with delayed umbilical cord separation (age >3 weeks) due to poor wound healing. However, this may not occur in patients with mild integrin defects. In these patients, presentation may occur in early childhood with recurrent skin (eg, cellulitis, omphalitis) and mucosal (eg, periodontitis) infections, reflecting the skin and oral mucosa's susceptibility to bacterial invasion. Infected tissue characteristically lacks purulence, as seen in this patient's history, and chronic infection can lead to ulceration and necrosis.
Serum studies show marked peripheral leukocytosis and neutrophilia, particularly during episodes of infection (reflecting impaired mobilization). Absolute lymphocyte and monocyte counts are normal, as seen in this patient. Biopsy of infected tissue shows inflammation but no neutrophils; culture often grows Staphylococcus aureus or gram-negative bacilli.
(Choice A) Adenosine deaminase deficiency is an autosomal recessive form of severe combined immunodeficiency characterized by deficient formation of mature B and T lymphocytes. As a result, patients have severe infections and failure to thrive, and laboratory studies show marked lymphopenia.
(Choice B) Patients with complement deficiencies are at increased risk for disseminated infection with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis). Cutaneous infections and neutrophilia are not seen.
(Choice C) Defective B-lymphocyte maturation occurs in X-linked (Bruton) agammaglobulinemia, which presents in infant boys with recurrent sinopulmonary and gastrointestinal infections, as well as with low B-cell and immunoglobulin concentrations. Periodontitis in a girl is inconsistent with X-linked agammaglobulinemia.
(Choice D) Chronic granulomatous disease (CGD) and Chédiak-Higashi syndrome (CHS) are characterized by defects in intracellular killing due to impaired respiratory burst and abnormal lysosomal trafficking, respectively. CGD presents in infant boys with infections from catalase-positive organisms (eg, S aureus, Serratia marcescens); Streptococcus pyogenes is catalase-negative and would be an unusual finding. CHS can cause skin infections; however, oculocutaneous albinism (eg, hypopigmented hair/skin, reflecting inadequate melanosome trafficking) and neutropenia (rather than neutrophilia) would be expected.
Educational objective:
Leukocyte adhesion deficiency presents with recurrent, nonpurulent skin and mucosal bacterial infections, as well as severe periodontal disease. Marked leukocytosis with a neutrophil predominance is common.