Oral Manifestations with Leukocyte Adhesion Deficiency: A Five Year Study 7/31/09

LUTHERAN MEDICAL CENTER
Dental Residency Program
Literature Review Form

Resident: Murphy Date: Region: Prov.
Article title: Oral Manifestations Associated w/ Leukocyte Adhesion Deficiency: A Five Year Study
Author(s): Roberts, MW, et al.
Journal: Pediatric Dentistry
Volume #; Number; Page #s): 12:2 4
Year: 1990
Major topic: Oral manifestations of LAD
Minor topic(s): LAD and its associated infections
Type of Article: Five year case study
Main Purpose: Assess how LAD affects the oral cavity, and how to treat it.
Overview of method of research: Five year case study of a 3 yo female w/ LAD

Findings: Leukocyte adhesion deficiency (LAD) occurs when three glycoproteins are absent or defective on leukocytes, leaving patients more susceptible to bacterial infections. The three sites are Mac-1, LFA-1, and gp 150,95. These proteins help the leukocyte to adhere to and phagocyte bacterium. Without them, the leukocytes defenses are severely diminished. LAD is an autosomal dominant disease that has been mapped to chromosome 21. Homozygous patients have severe LAD, while heterozygous patients usually present as clinically healthy. People with LAD lack a necessary beta subunit, which activates and alpha subunit, which further affects immunosuppression. The earliest clinical manifestation of LAD is delayed separation of the umbilical cord, causing septicemia. Other infections occurring in people with LAD include multiple skin abscesses, recurrent ear infections, and pneumonitis. While lab results show elevated levels of granulocytes, biopsy sites of infected areas are absent of neutrophils. The most common oral finding with LAD is severe periodontitis. Other oral findings include stomatitis, ulcers, and facial cellulites. The five year case study was on a three yo old female(child’s parents were first cousins) who presented with a history of respiratory distress, fever, poor healing, recurrent skin infections, multiple abscesses without pus, and leukoctyosis. Her WBC was 10-20,000ml. After multiple diagnostic tests, it was confirmed by fluorescent cell analysis that she lacked the necessary receptors on her leukocytes. She had generalized gingival recession, increased mobility, and attachment and bone loss. The child was treated with thorough scaling and prophy. The parents were advised to brush the child’s teeth twice daily with sodium bicarbonate and to apply stannous fluoride .4% after the evening hygiene, every night. The patient was also placed on prophy. Trimethoprim, Septra, and ferrous sulfate were prescribed. Seven months later the child returned with better oral hygiene practices, but still generalized gingivitis. There was increasing bone loss associated with all of the primary teeth. OHI was reinforced and the patient was sent home. Four months later, now eleven months since the original visit, the child presented with a large, asymptomatic, facial swelling of the mandibular left molars of three day duration. Both teeth had abscesses. The area was irrigated extensively and the child was placed on more antibiotics. At six years 8 months she was diagnosed with chronic progressive periodontitis. The girl returned to the hospital 6 more times before her eight birthday with serious infections and no improvement of her periodontal disease. Every time she presented asymptomatically. The basic treatment regiment included constant antibiotic therapy and extensive oral hygiene practices, all to simply curtail the periodontal disease.

Key points in the article discussion: LAD is effectively characterized by the patients inability to respond to recurrent infections. The leukocytes have the severe functional defect which prevents them from phagocytic chemotaxis, aggregation, and adherence. When cultures were obtained from the patients periodontal pockets, the usual suspect of periodontal disease were not present(a,a, p.g, etc.). This is probably due to the problem not being with the childs bacterial count, but the inability to fight off many if not all of the opportunistic pathogens. Intense oral hygiene and constant professional care failed to arrest the periodontal disease. The child still presented with attachment and bone loss and destruction of the surrounding periodontal tissue. Antibiotics and the use of stannous fluoride .4% only suppressed the disease, with the antibiotics being more effective.

Summary of conclusions: The maintenance of healthy gum tissue depends largely on an intact immune system. You can practice the best oral hygiene in the world, but if you can’t fight the bacteria off at a basic level, it’s futile. This is what patients with LAD deal with daily. Possible treatment options include extraction of all primary teeth to attempt to get the oral tissue to a healthy baseline, bone marrow transplant, and as previously stated, constant aggressive antibiotic and OHI therapy.

Assessment of article: Good article. Very informative and detail oriented. It was a bit of a downer, essentially stating that so far, there is no concrete way to help individuals affected by this terrible disease get better. One bad thing about the article, it only mentioned patient compliance briefly. I thought they should have focused more efforts on making sure the treatment was being followed to the “T” at home.

Hemophilia A

Department of Pediatric Dentistry

Lutheran Medical Center

Date: 07/24/2009

Article title: Hemophilia A

Author(s): Leon W. Hoyer M.D.

Journal: New England Journal of Medicine

Volume (number): Vol 330 No 1

Month, Year: 1994

Major topic: Hemophilia

Minor topics:

Type of Article: Review of Literature

Main Purpose: Review of Everything Hemophilia A

Overview of method of research: Review of Literature

Findings:

Hemophilia has a history of being a very destructive disease, but modern therapies have significantly improved the quality of life and the lifespan of those affected. Basically, it is the absence of clotting factor VIII or having a plasma concentrate of less than .04ug per milliliter plasma. Treatment is much more than the simple prescription of factor VII concentrates. A dental examination with plans for appropriate care is recommended as an essential part of any hemophilia patient's treatment.

Key points/Summary :

• Incidence approaches 20 per 100,000 male births.
• Although and X-linked disorder, it is supposed that up to 1/3 of cases come from random deletions and are not inherited.
• The gene that codes for factor VIII is at the tip of the long arm of the X chromosome, which can be missing or mutated.
• Factor VIII circulates in a non-covalent bond with von WIllenbrand factor, which enhances synthesis of the factor.
• Factor VIII is essential for rapid cleavage of factor X--if you want more clotting science, read it.
• Clinically, it is essential to distinguish between severe presentations and mild or moderate, the later perhaps never having a bleeding episode outside of surgery or severe trauma.
• Diagnosis of hemophilia should be suspected anytime there is abnormal bleeding in male patients. The diagnosis is determined by laboratory testing (which you can read about in the article)
• The clinical hallmarks are joint and muscle hemorrhages, easy bruising and prolonged and potentially fatal hemorrhage post surgery or trauma; but no excessive bleeding after minor cuts and abrasions.
• Hemarthroses are usually first noted when a child is learning to walk, which quickly leads to limitation of motion and mild discomfort. Within hours, it becomes severe pain, joint swelling and cutaneous warmth.
• Untreated the disease process leads to hemophilic arthropathy and can lead to permanent disability.
• Bleeding can happen in other locations also including intramuscular hematomas and closed space bleeding can lead to nerve paralysis and or airway constriction.
• In the past, 25% of deaths were attributed to intracranial bleeds. AIDS would take over this high percentage of deaths during the years of tainted transfusion.
• Factor VIII plasma replacement can be achieved using human donated plasma or synthetically derived alternatives.
• Patients with some factor VIII production can benefit from Desmopressin.
• Today--1994 that is--parents can use genetic testing and amniocentesis to determine the likelihood of transmission from mother to son.
• Care is constantly improving and the article suggested that perhaps stem-cell therapy could ultimately be a cure for the disease.

Assessment of article: A great review. This article was too in-depth for our uses and it would be nice to see an update to this (which I'm sure could be researched) and see where treatment is today. This is an interesting and significant disease. If you can get through the hard science without burning out there is a lot of good relevant information.