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Kostmann Disease Follow-up

  • Author: Peter N Huynh, MD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Aug 31, 2015
 

Further Outpatient Care

Obtain a CBC count with differential twice per week during the first 4 weeks after the initiation of granulocyte-colony stimulating factor (G-CSF) or for 2 weeks following any dosage adjustments. Thereafter, obtain a CBC count with differential monthly for 6 months. When the minimum daily dose is found, the maintenance phase can be started, with monitoring of absolute neutrophil counts every 3-6 months.

Routine clinical follow-up every 3 months for patients who are stable is recommended.

Enroll patients in the Severe Chronic Neutropenia International Registry (SCNIR).

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Further Inpatient Care

Patients admitted for inpatient care related to infection warrant blood, urine, and infectious-site cultures, as well as chest radiography, as clinically indicated. Aggressive intravenous antibiotic therapy and appropriate supportive therapies should be initiated. Consultation with pediatric immunologist, pediatric hematologist, and infectious diseases specialist is recommended.

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Transfer

Once severe congenital neutropenia is suspected, patient should be referred to a specialized treatment center regarding genetic testing and treatment.

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Deterrence/Prevention

Provide genetic counseling to parents of infants because Kostmann disease has an autosomal recessive form of inheritance. Other disorders of severe congenital neutropenia demonstrate several modes of inheritance, including autosomal recessive, autosomal dominant, sporadic, and X-linked forms.

Maintaining an adequate absolute neutrophil count (≥1000/μL) with G-CSF is central to preventing infections.

Annual bone marrow examination for morphology and cytogenetic testing should be performed in order to identify any changes indicating malignant transformation and to allow for early intervention with bone marrow transplantation.

Regular G-CSF receptor analysis should be performed to identify mutations. This can be done on either peripheral blood or bone marrow samples by laboratories headed by the SCNIR.

Regular dental and periodontal evaluation and care should be performed in order to minimize dental complications. The characteristic gingivitis and periodontal disease persist even after G-CSF.

Isolating patients within their homes or away from crowds has shown little practical value.

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Complications

Most complications relate to infections.[27]

Bone demineralization occurs in approximately 50% of patients, which may result in bone pain and unusual fractures, either as a part of the pathophysiology of the disease or potentially from either endogenous or exogenous G-CSFs by increased bone resorption.

About 1 in 5 patients with severe congenital neutropenia develop secondary malignancies. The incidence of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in severe congenital neutropenia after 10 years of G-CSF treatment is 21%. Acquired mutations in G-CSF receptor CSF3R are a highly predictive marker for the progression of severe congenital neutropenia to leukemia.[14] Of patients with severe congenital neutropenia, 20-30% have acquired mutations in the CSF3R gene, which produce C-terminally truncated hyperresponsive forms of the G-CSFRhyper and a strong predisposition for MDS and AML.

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Prognosis

In the 1950s, almost all patients would die of sepsis, cellulitis, or pneumonia within the first 2 years of life. In the 1960s and 1970s, more antibiotic therapy was used and lethal infections were less frequent.

In the 1970s, survival with severe congenital neutropenia started to improve owing to antibiotic prophylaxis and to curative parenteral antimicrobial chemotherapy.

Since 1987, the use of G-CSF has resulted in fewer infections of shorter duration. This has dramatically improved patient's quality of life and prolongs survival. However, G-CSF and neutrophil recovery does not improve chronic stomatitis or gingivitis, and tooth loss can occur.

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Patient Education

Educate patients and their families on the signs and symptoms of infections to ensure appropriate and prompt therapy.

Inform patients and their families of the risk for developing leukemia.

The Immune Deficiency Foundation is an important resource for education and support for patients and families with any primary immunodeficiency disease. The telephone number is 1-800-296-4433. The Web site is www.primaryimmune.org. The foundation's mailing address is 40 W Chesapeake Ave, Suite 308, Towson, MD 21204; some states have local chapters.

The Jeffrey Modell Foundation, at 747 3rd Avenue, New York, NY 10017, also provides educational support. The telephone number is 1-866-INFO-4-PI. The Web site is www.jmfworld.org.

The SCNIR was established in March 1994, in the United States, Australia, Canada, and the European Community. The SCNIR is directed by a scientific advisory board of physicians from around the world who care for severe congenital neutropenia patients. Their mission is to establish a worldwide database of treatment and disease-related outcomes for persons diagnosed with severe chronic neutropenia. Collection of this information will lead to improved medical care and is used for research to determine the causes of neutropenia. The Web site is www.depts.washington.edu/registry.

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Contributor Information and Disclosures
Author

Peter N Huynh, MD Chief of Allergy and Immunology, Kaiser Permanente, Panorama City Medical Center

Peter N Huynh, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Stuart Min, MD Allergist in private practice

Stuart Min, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Karine Zakarian, MD Fellow in Allergy and Immunology, LAC+USC Medical Center

Karine Zakarian, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD 

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, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

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 Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

James M Oleske, MD, MPH François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, Rutgers New Jersey Medical School; Professor, Department of Quantitative Methods, Rutgers New Jersey Medical School

James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Allergy Asthma and Immunology, American Academy of Hospice and Palliative Medicine, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, Pediatric Infectious Diseases Society, Arab Board of Family Medicine, American Academy of Pain Management, National Association of Pediatric Nurse Practitioners, Association of Clinical Researchers and Educators, American Academy of HIV Medicine, American Thoracic Society, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

Michael S Tankersley, MD, FAAAAI, FACAAI, FAAP Program Director, Allergy and Immunology Fellowship; Division Chief, Allergy and Immunology, Department of Medicine, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, Texas

Michael S Tankersley, MD, FAAAAI, FACAAI, FAAP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, and Joint Council of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

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