Pediatric Complement Receptor Deficiency Clinical Presentation

Updated: Dec 19, 2016
  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Presentation

History

The 5 subtypes of leukocyte adhesion deficiency (LAD) 1 depend on the level of messenger RNA (mRNA) CD18 expression, the level of CD18 protein expression, and the clinical severity. [8] In subtypes 1 and 4 of LAD 1, there is absence of CD11/CD18 expression and patients have severe life-threatening infections (see Table 4). In subtypes 2, 3, and 5 of LAD type 1, diminished CD11/CD18 (3-10% of normal) is observed; however, the patients have less severe infections and chronic periodontitis. Initial reports described LAD as delayed separation of the umbilical cord (after 21 d or longer). Delayed separation of the umbilical cord is observed in the severe form of LAD type 1 but may not occur in the milder forms or in LAD type 2.

The hallmark of LAD type 1 is infection without pus and inflammatory response. The immune defect in LAD type 1 results in decreased neutrophil inflammatory responses and decreased cellular cytotoxicity. The types of infections and susceptibility to microorganisms resemble other neutrophil defects. Onset of infections somewhat varies. In the severe form of LAD type 1, infections often have an onset by age 3-4 months. In milder phenotypes of LAD type 1, onset of infections may be delayed. The most common infections in both phenotypes are otitis media, ulcerative stomatitis, gingivitis, periodontitis, and skin subcutaneous abscesses. Periodontitis and gingivitis are the principal infections observed in LAD type 2.

Guidelines for the diagnosis and management of primary immunodeficiencies have been established. [23]

  • Patients with LAD have the following types of infections:

    • Necrotic cutaneous abscesses and cellulitis

    • Mucosal and perirectal abscesses

    • Omphalitis

    • Periodontitis, leading to gingival hyperplasia and loss of alveolar bone and teeth

    • Gingivitis

    • Otitis media

    • Pneumonia

    • Peritonitis

    • Necrotizing enterocolitis

    • Intestinal ulceration

    • Aseptic meningitis

  • Patients with LAD are susceptible to a wide spectrum of gram-positive and gram-negative bacteria, most commonly Staphylococcus aureus, Pseudomonas species, enterobacteria, and Candida albicans.

  • In LAD type 2, other problems include severe mental retardation, short stature, and distinctive facial features. The facial features include long eyelashes and a broad and depressed nasal bridge.

  • In LAD type 3, the clinical manifestations are similar to that seen in LAD type 1, but there is also a bleeding tendency due to abnormal platelet aggregation.

  • In E-selectin deficiency, mild neutropenia is observed instead of the marked leukocytosis found in other types of LAD.

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Physical

Physical examination findings are those of infections. Infectious sites are typically devoid of inflammatory cells. Signs of inflammation, such as erythema, are absent. In addition, pus is absent in infected drainages. Indolent and necrotic abscesses and cellulitis occur. Gingivitis and periodontitis occur in all the types of LAD. Another hallmark of LAD is poor wound healing. This may lead to the formation of a characteristic paper-thin bluish scar. Lymphoid tissue is normal in size.

Children with LAD type 2 have severe mental retardation, distinctive facies, and short-limbed dwarfism. The facial features include flat face, long eyelashes, broad and depressed nasal bridge, and anteverted nostrils. The palms of the hands are broad, dorsally positioned second toes were reported in one patient, and a simian crease may be present.

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Causes

LAD type 1 is an autosomal recessive immunodeficiency disorder affecting the CD11/CD18 complex. Defects in the beta chain result in the absence, insufficient amount, or abnormal function of the common CD18 unit.

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