Pediatric Complement Receptor Deficiency Treatment & Management

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

Medical Care

In the severe phenotype of leukocyte adhesion deficiency (LAD) type 1, the prognosis for long-term survival is poor. [8] Immune reconstitution with hematopoietic stem cell transplantation is the treatment of choice. [24, 25, 26, 27] Numerous stem cell donor choices, human leukocyte antigen (HLA)–matched related bone marrow, HLA-matched cord blood, and HLA-matched unrelated bone marrow, have been successfully used to immune reconstitute patients with LAD type 1. Preexisting infections, which are common, must be successfully treated before transplantation. Patients with preexisting infections may need surgical drainage, debridement, and intravenous antibiotics.

The bone marrow in patients with LAD is hyperplastic, and some T-cell function is present. Therefore, myeloablative treatment to make room in the bone marrow and immunosuppressive therapy to prevent graft rejection has been used. The absence of LFA-1 on host's cells that cause decreased T-cell function, T-cell cytotoxicity, and natural killer (NK) cell cytotoxicity may actually facilitate engraftment. Both acute and chronic graft versus host disease (GVHD) have been a problem in patients with LAD even when an HLA-matched sibling donor is used.

  • Treatment of infections in patients with the severe phenotype of LAD type 1 can be difficult.

    • Treatment often requires appropriate intravenous antibiotics.

    • Surgical drainage of abscesses and surgical debridement of infected necrotic tissue is often required.

    • Some patients have undergone amputation of limbs to control infected bone.

    • The gingivitis and periodontitis that occurs in all forms of LAD often requires surgery, sometimes with removal of dentition.

    • Because of poor wound healing, complications such as fistulas may occur. Therefore, surgical care is complex as well.

    • Infections in patients with the moderate phenotype of LAD type 1 can often be treated with oral antibiotics.

    • Mellouli et al reported successful granulocyte transfusions in a patient with LAD1 who had Fusariumsolani ecthyma gangrenosum. [28] The patient had received antifungal and antibacterial therapy, which did not clear his infections. Then the patient received irradiated phenotyped granulocyte transfusions along with G-CSF and continued antifungal therapy over 5 months. This resolved the infection.

  • LAD type 2 is a metabolic defect of fucose metabolism that affects all fucosylated molecules, including sialyl-Lewis X, which is deficient in LAD type 2.

    • The biochemical activity of GDP-D-mannose-4,6 dehydratase (GMD) that converts mannose to fucose is decreased in patients with LAD type 2. However, the primary defect is thought to be a GMD-regulating protein.

    • Erythrocyte fucosylated H antigens are also absent in LAD type 2 (Bombay phenotype).

  • Oral fucose supplementation has been successful in the treatment of patients with LAD type 2, with correction of expression CD15s on neutrophils. [12] Elevated neutrophil cell counts returned to the reference range, and clinical improvement was achieved with reduction of infections.

    • Patients with LAD type 2 were treated with 5 doses of fucose per day, starting at 25 mg/kg, which was slowly increased to 492 mg/kg.

    • After 40 days of fucose 140 mg/kg, levels of E-selectins, P-selectins, and CD15s reached approximately 50% the reference range.

    • Neutrophil counts decreased to the reference range.

    • H antigens on erythrocytes did not reappear.

    • Of importance, psychomotor development may also improve.

  • Treatment of LAD type 3 can be difficult. Because of the thrombocytopenia and bleeding problems, these patients require frequent transfusions. The only possible curable therapy is bone marrow transplantation, which so far has not been very encouraging. [29]

Next:

Surgical Care

Consultation with an oral surgeon is necessary for most patients with any form of LAD. Consultation with a surgeon for surgical drainage and necrotic tissue debridement is ordered as indicated for patients with LAD.

Previous
Next:

Consultations

Diagnosis and management of LAD should be referred to a hematologist and/or an immunologist. A hematologist or an immunologist skilled in bone marrow transplantation should perform this procedure.

Consultation with an oral surgeon is necessary for most patients with any form of LAD. Consultations to obtain appropriate cultures are often needed. This may include a pulmonologist to perform bronchoalveolar lavage (BAL), a surgeon to perform abscess aspirates, and an otolaryngologist to perform myringotomy or sinus aspirates. Consultation with an infectious diseases specialist may be indicated to select appropriate antibiotic coverage.

Previous
Next:

Diet

In LAD type 1, no dietary restrictions are necessary. In LAD type 2, fucose dietary supplementation is indicated.

Previous
Next:

Activity

Activity is not restricted.

Previous