eMedicine Specialties > Pediatrics: General Medicine > Hematology

Shwachman-Diamond Syndrome: Treatment & Medication

Author: Antoinette C Spoto-Cannons, MD, FAAP, Associate Professor, Department of Pediatrics, Director, Undergraduate Children's Health Care Education, University of South Florida College of Medicine
Coauthor(s): Jessica Marie Keshishian, MD, Resident Physician, Department of Pediatrics, University of South Florida; Sarah Syed, University of South Florida College of Medicine; Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Contributor Information and Disclosures

Updated: Sep 30, 2009

Treatment

Medical Care

The goals of Shwachman-Diamond syndrome (SDS) treatment include (1) pancreatic enzyme supplementation, (2) prevention or treatment of serious and/or invasive infections with early attention to febrile illnesses, (3) correction of hematologic abnormalities when possible, and (4) prevention of orthopedic deformities.

  • A significant proportion of patients with Schwachman-Diamond syndrome require pancreatic enzymes, a low-fat diet, multivitamins, and fat-soluble vitamins; however, the needs of these patients may decrease with age. Treatment of pancreatic insufficiency only slightly improves growth.37 .
  • When patients with Schwachman-Diamond syndrome experience an acute febrile illness, obtain bacterial cultures because of the increased risk of sepsis from the neutrophil migrational defect with or without neutropenia observed in these patients. Empiric treatment with parenteral broad-spectrum antibiotics may be indicated. Additionally, prophylactic antibiotics may be necessary to help prevent infection.
  • No therapy has been successful in completely reversing neutropenia, anemia, or thrombocytopenia.37
  • Neutropenia may be treated by granulocyte colony-stimulating factor (GCSF). However, its risk of accelerating the development of myeloproliferative disorders remains to be determined.
  • Lithium and thiamine were used in the past to improve chemotactic performance;46,22,47 however, their use has fallen out of favor since the advent of recombinant growth factor in the 1990s.
  • Neutropenia has not been improved by the administration of fresh frozen plasma, vitamin B-12, folic acid, pyridoxine, riboflavin, methionine, prednisolone, anabolic steroids, vitamin A, vitamin E, or pancreatic extract.23
  • Anemia and thrombocytopenia may require repeated transfusions if the patient is symptomatic. Additionally, erythropoietin may be beneficial in the treatment of anemia.
  • Lymphoproliferative and myeloproliferative malignancies and aplastic marrow observed in patients with Schwachman-Diamond syndrome are usually unresponsive to standard chemotherapy and require allogenic hematopoietic stem cell transplantation.25,48 These patients are at high risk for complications after bone marrow transplant. Numerous factors may contribute to this high complication rate. Their underlying hematologic abnormalities and high reported rate of nonspecific organ malfunctions may place them at higher risk for the development of toxicities.49 In an attempt to reduce toxicity, preparative regimens avoiding the combination of busulfan and cyclophosphamide have been tried.50 Reduced-intensity conditioning was associated with excellent donor cell engraftment and modest morbidity.51
  • Growth hormone has been used to treat children with Schwachman-Diamond syndrome who have growth hormone deficiency. The initial response is good; however, long-term therapy with growth hormone is unsuccessful.52
  • Appropriate orthopedic follow-up of metaphyseal dysplasia may prevent deformities.

Consultations

  • Pediatric gastroenterologist - For management of pancreatic insufficiency
  • Pediatric endocrinologist - For pancreatic insufficiency, short stature, and delayed puberty
  • Pediatric immunologist - For neutropenia, neutrophil migrational defects, and immunoglobulin deficiencies
  • Pediatric oncologist - For routine bone marrow aspirations, which are indicated for early detection of aplasia and lymphoproliferative and myeloproliferative malignancies
  • Pediatric infectious diseases specialist - To help treat unusual infections that may occur from neutropenia and a neutrophil migrational defect
  • Clinical geneticist - For parent counseling and chromosome studies
  • Pediatric orthopedic surgeon - To manage skeletal abnormalities (Special attention is required for metaphyseal dysplasia because of the risk of significant deformities, particularly in knees and hips.)

Diet

  • A low-fat diet may be necessary depending on the degree of malabsorption.

Activity

  • No limitations on activity are necessary for individuals with Schwachman-Diamond syndrome, unless thrombocytopenia is observed.

Medication

Pancreatic enzymes

These agents are used to replace endogenous pancreatic enzymes.


Pancrelipase (Creon, Ku-Zyme, Pancrease, Viokase, Ultrase)

Assists in digestion of protein, carbohydrates, and fats. Dosage recommendations are only approximations for initial dosages. Actual dose depends on digestive requirement of individual patient.

Adult

Pediatric

6-12 months: 2000-4000 IU per 120 mL of formula
1-6 years: 4000-8000 IU with meals; 4000 IU with snacks
7-12 years: 4000-12,000 IU with meals and snacks

Calcium carbonate and magnesium hydroxide decrease effect of pancreatic enzymes, while H2 antagonists (eg, ranitidine, cimetidine) increase effects of enzymes

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Doses >6000 U/kg per meal may be associated with fibrosing colonopathy, which has been evident in patients with CF who developed strictures of the ascending colon; inactivated by acids (use microencapsulated products whenever possible because these products permit better dissolution of enzymes in the duodenum and protect enzyme preparations from acid degradation in stomach); adverse reactions include nausea, cramps, constipation, diarrhea, lacrimation, sneezing, rash, bronchospasm, and shortness of breath; high doses may cause hyperuricemia and hyperuricosuria

Colony-stimulating factors

These agents provide red cell line stimulation.


Epoetin alfa (Epogen, Procrit)

FDA approved for treatment of chronic anemia. Stimulates division and differentiation of committed erythroid progenitor cells; induces release of reticulocytes from bone marrow into bloodstream. SC route provides sustained serum levels compared to IV route. Reduce dose when hematocrit reaches target range of 30-36% or hematocrit increases >4 points over any 2-wk period. Hold dose if hematocrit >36%.

Adult

50-150 U/kg IV/SC 3 times per wk

Pediatric

Administer as in adults; individualize to maintain hematocrit within 30-36% of target range; increase 25-50 U/kg 3 times per wk q4-6wk if hematocrit does not increase by 5-6 points after 8 wk of therapy and hematocrit is below target range; increase dose until desired response, not to exceed 300 U/kg 3 times per wk

Documented hypersensitivity; uncontrolled hypertension; neutropenia in newborns

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in porphyria, hypertension, and history of seizures; decrease dose if hematocrit increases >4 U in any 2-wk period; monitor hematocrit, blood pressure, clotting times, platelets, BUN, and serum creatinine levels; prior to and during therapy, evaluate iron stores by obtaining serum iron, ferritin, and total iron-binding capacity; may cause hypertension, seizures, fever, headaches, edema, rash, urticaria, dizziness, fatigue, chest pain, cough, nausea, vomiting, diarrhea, clotted access, arthralgia, weakness, myocardial infarction, stroke, transient ischemic attack, and rarely neutropenia


Filgrastim (Neupogen)

FDA approved for severe chronic neutropenia.
GCSF activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils. If IV route is used and GCSF final concentration is <15 mcg/mL, add 2 mg of albumin/mL to prevent drug adsorption to administration set.

Adult

5 mcg/kg/d SC

Pediatric

5-10 mcg/kg per dose IV/SC qd for 14 d or until ANC reaches acceptable level, which varies from patient to patient; not to exceed 480 mcg/d

Do not use 12-24 h before or 24 h after administering cytotoxic chemotherapy because it increases sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Risk of developing myelodysplastic syndrome or acute myeloid leukemia in certain patients; leukocytosis; possible tumor growth; monitor CBC count, uric acid, and LFTs; caution in patients with malignancies with myeloid characteristics and in patients with gout or psoriasis; may cause bone pain, osteoporosis, fever, rash, pain at injection site, thrombophlebitis, anaphylactic reaction, increased alkaline phosphatase, reversible increase in uric acid and lactate dehydrogenase, splenomegaly, leukocytosis, thrombocytopenia, chest pain, hematuria, proteinuria, headache, weakness, supraventricular arrhythmias, transient decrease in blood pressure, and pericarditis

Vitamins

Vitamins are essential for normal DNA synthesis and cell function.


ADEK vitamins (ADEKS)

PO multinutrient specially formulated for use under medical supervision to provide nutritional supplementation in individuals with malabsorptive conditions. Each dose contains water-miscible forms of fat-soluble vitamins A, D, E, and K plus other nutrients, including vitamin C, B-complex vitamins, biotin, folic acid, and zinc. Available as chewable tab or pediatric drops.

Adult

Pediatric

<12 months: 1 mL PO qd
1-3 years: 2 mL PO qd
4-10 years: 1 tab PO qd
>10 years: 2 tabs PO qd

Best administered with supplementary pancreatic enzymes for individuals requiring enzyme therapy for control of steatorrhea or improved fat absorption; vitamin K interferes with actions of anticoagulant drugs

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Do not exceed recommended doses; contraindicated in pregnancy if vitamin A exceeds RDA; exclude pernicious anemia before using because folic acid in doses >0.1 mg/d may mask symptoms; for chewable tab, chew or crush tab thoroughly before swallowing

More on Shwachman-Diamond Syndrome

Overview: Shwachman-Diamond Syndrome
Differential Diagnoses & Workup: Shwachman-Diamond Syndrome
Treatment & Medication: Shwachman-Diamond Syndrome
Follow-up: Shwachman-Diamond Syndrome
Multimedia: Shwachman-Diamond Syndrome
References
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  86. Yamaguchi M, Fujimura K, Toga H, et al. Shwachman-Diamond syndrome is not necessary for the terminal maturation of neutrophils but is important for maintaining viability of granulocyte precursors. Exp Hematol. Apr 2007;35(4):579-86. [Medline].

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Further Reading

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Keywords

Shwachman-Diamond syndrome, SDS, bone marrow dysfunction, pancreatic insufficiency, short stature, congenital lipomatosis of pancreas, metaphyseal dysplasia, pancreatic hypoplasia, marrow dysfunction, pancreatic hypoplasia, marrow dysfunction, metaphyseal dysplasia, Shwachman-Bodian syndrome, Shwachman-Diamond-Oski-Knaw syndrome, cystic fibrosis, Fanconi anemia, Blackfan-Diamond, skeletal dysplasia, osteoporosis, upper respiratory tract infections, otitis media, sinusitis, pneumonia, aphthous stomatitis, skin infections, paronychia, osteomyelitis, bacteremia, myelodysplastic syndrome, MDS, leukemia, malabsorption, imperforate anus, Hirschsprung disease, constipation, diarrhea, hearing loss, tooth enamel defects, hypomaturation, hypocalcification, hypoplasia, treatment, diagnosis

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Contributor Information and Disclosures

Author

Antoinette C Spoto-Cannons, MD, FAAP, Associate Professor, Department of Pediatrics, Director, Undergraduate Children's Health Care Education, University of South Florida College of Medicine
Antoinette C Spoto-Cannons, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, Council on Medical Student Education in Pediatrics, and Florida Pediatric Society
Disclosure: Nothing to disclose.

Coauthor(s)

Jessica Marie Keshishian, MD, Resident Physician, Department of Pediatrics, University of South Florida
Jessica Marie Keshishian, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Student Association/Foundation, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

Sarah Syed, University of South Florida College of Medicine
Sarah Syed is a member of the following medical societies: American Medical Student Association/Foundation
Disclosure: Nothing to disclose.

Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Mudra Kumar, MD, MBBS, MRCP is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Sharada A Sarnaik, MBBS, Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan
Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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