eMedicine Specialties > Dermatology > Pediatric Diseases

Chediak-Higashi Syndrome

Roman Janusz Nowicki, MD, PhD, Associate Professor, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland

Updated: May 29, 2009

Introduction

Background

Chédiak-Higashi syndrome (CHS) was described by Beguez Cesar in 1943, Steinbrinck in 1948, Chédiak in 1952, and Higashi in 1954. Chédiak-Higashi syndrome is a rare childhood autosomal recessive disorder that affects multiple systems of the body. Patients with Chédiak-Higashi syndrome exhibit hypopigmentation of the skin, eyes, and hair; prolonged bleeding times; easy bruisability; recurrent infections; abnormal natural killer cell function; and peripheral neuropathy. Morbidity results from patients succumbing to frequent bacterial infections or to an accelerated-phase lymphoproliferation into the major organs of the body. Most patients who do not undergo bone marrow transplantation die of a lymphoproliferative syndrome, although some patients with Chédiak-Higashi syndrome have a relatively milder clinical course of the disease.^1,2,3

Pathophysiology

Chédiak-Higashi syndrome is an autosomal recessive immunodeficiency disorder characterized by abnormal intracellular protein transport. The Chédiak-Higashi syndrome gene was characterized in 1996 as the LYST or CHS1 gene and is localized to bands 1q42-43. The CHS protein is expressed in the cytoplasm of cells of a variety of tissues and may represent an abnormality of organellar protein trafficking.^4,5

The Chédiak-Higashi syndrome gene affects the synthesis and/or maintenance of storage/secretory granules in various types of cells. Lysosomes of leukocytes and fibroblasts, dense bodies of platelets, azurophilic granules of neutrophils, and melanosomes of melanocytes are generally larger in size and irregular in morphology, indicating that a common pathway in the synthesis of organelles responsible for storage is affected in patients with Chédiak-Higashi syndrome. In the early stages of neutrophil maturation, normal azurophil granules fuse to form megagranules, whereas, in the later stage (ie, during myelocyte stage), normal granules are formed. The mature neutrophils contain both populations. A similar phenomenon occurs in monocytes. The impaired function in the polymorphonuclear leukocytes may be related to abnormal microtubular assembly.

The disease is often fatal in childhood as a result of infection or an accelerated lymphomalike phase; therefore, few patients live to adulthood. In these patients, a progressive neurologic dysfunction may be the dominant feature. Neurologic involvement is variable but often includes peripheral neuropathy. The mechanism of peripheral neuropathy in Chédiak-Higashi syndrome has not been completely elucidated. Both the axonal type and the demyelinating type of peripheral neuropathy associated with Chédiak-Higashi syndrome have been reported.

Defective melanization of melanosomes occurs in oculocutaneous albinism associated with Chédiak-Higashi syndrome. In melanocytes, autophagocytosis of melanosomes occurs.

Most patients also undergo an accelerated phase or accelerated reaction, which is a nonmalignant lymphohistiocytic lymphomalike infiltration of multiple organs that occurs in more than 80% of patients. This lymphomalike stage is precipitated by viruses, particularly by infection by the Epstein-Barr virus. It is associated with anemia, bleeding episodes, and overwhelming infections leading to death. Infections most commonly involve the skin, the lungs, and the respiratory tract and are usually due to Staphylococcus aureus, Streptococcus pyogenes, and Pneumococcus species.

Frequency

United States

Chédiak-Higashi syndrome is rare.

International

Chédiak-Higashi syndrome is rare.⁶

Mortality/Morbidity

Death often occurs in the first decade as a result of infection, bleeding, or development of the accelerated lymphomalike phase, but survival into the second and third decades has been reported.

Race

Chédiak-Higashi syndrome affects all races. Al-Khenaizan suggests that Chédiak-Higashi syndrome may be underreported in persons of darker-skinned races.⁷

Age

Symptoms of Chédiak-Higashi syndrome usually appear soon after birth or in children younger than 5 years.

Clinical

History

• Infants born with Chédiak-Higashi syndrome have nonpigmented skin (similar to albinos but in patchy distribution), blonde hair, and blue eyes.
• Signs and symptoms that usually appear soon after birth include the following:
  • Adenopathy
  • Aphthae
  • Gingivitis
  • Hyperhidrosis
  • Miliaria
  • Jaundice
  • Severe and extensive pyoderma
  • Recurrent sinopulmonary infections
  • Fever unrelated to recognizable infection

Physical

• Oculocutaneous albinism is prominent, and, together with photophobia and silvery hair, it is helpful in early diagnosis. The skin is fair, the retinae are pale, and the irides are translucent. The hair is light blonde or silvery gray and may be sparse.
• In Chédiak-Higashi syndrome, patients are affected by frequent and severe pyogenic infections secondary to abnormal functioning of polymorphonuclear leukocytes, which is associated with albinism and a bleeding tendency.
• Recurrent skin infections occur frequently and range from superficial pyoderma to deep subcutaneous abscesses and ulcers that heal slowly and result in atrophic scars. S aureus is the most common causative agent. Deep ulcerations resembling pyoderma gangrenosum have also been described.
• The complete syndrome includes oculocutaneous albinism with photophobia, neurologic features, recurrent infections, and enterocolitis.
• Lymphadenopathy and hepatosplenomegaly are variable.
• Severe gingivitis and oral mucosal ulceration are common. Oral ulcerations and periodontal disease also occur.^8,9
• Chédiak-Higashi syndrome may present with neurologic dysfunction and should be considered in the differential diagnosis of children and young adults first seen with symptoms of spinocerebellar degeneration or movement disorders.
  • Common physical findings include abnormal gait, clumsiness, seizures, paresthesia, mental retardation, and peripheral neuropathy.
  • In many persons with Chédiak-Higashi syndrome, neurologic changes appear in the lymphoproliferative lymphomalike phase.
  • Progressive neurologic deterioration is common in patients who survive early childhood. Generally, such patients eventually enter an accelerated phase of the disease with widespread infiltration by lymphocytes and histiocytes, causing rapid enlargement of the liver, the spleen, and the lymph nodes, and with concurrent severe leukopenia and thrombocytopenia, resulting in death from infection or bleeding.
• The adult form of Chédiak-Higashi syndrome manifests during late childhood to early adulthood and is marked by various neurologic sequelae, including parkinsonism, dementia, spinocerebellar degeneration, and peripheral neuropathy.

Causes

• The underlying defect in Chédiak-Higashi syndrome remains elusive, but the disorder can be considered a model for defects in vesicle formation, fusion, or trafficking.
• Chédiak-Higashi syndrome is inherited in an autosomal recessive pattern. Parental consanguinity is often reported.
  • The Chédiak-Higashi syndrome locus on human chromosome 1 encodes a lysosomal trafficking regulator, formerly termed LYST (currently termed CHS1), which is defective in patients with CHS.^10,11
  • Patients with Chédiak-Higashi syndrome exhibit alterations in neutrophils. These alterations include neutropenia, which may be profound; decreased deformability, resulting in impaired chemotaxis; and delayed phagolysosomal fusion, resulting in impaired bactericidal activity.

Differential Diagnoses

Albinism
Bacterial Mouth Infections
Cutaneous T-Cell Lymphoma
Griscelli Syndrome
Pyoderma Gangrenosum

Other Problems to Be Considered

Postinflammatory hypopigmentation
Poliosis
Leukemia¹²
Griscelli-Prunieras syndrome¹³

Workup

Laboratory Studies

• Peripheral blood smear: Diagnosis of Chédiak-Higashi syndrome is made by recognition of the characteristic giant granules in neutrophils, eosinophils, and granulocytes by using light microscopy of a routine blood smear. Laboratory findings include neutropenia and hypergammaglobulinemia.
• Bone marrow smears: Bone marrow smears reveal giant inclusion bodies in leukocyte precursor cells. The granules are peroxidase positive and contain lysosomal enzymes, suggesting that they are giant lysosomes, or in the case of melanocytes, that they are giant melanosomes. The diagnostic hallmark is the occurrence of giant inclusion bodies in the peripheral leukocytes and their bone marrow precursors.¹⁴
• Fluorescence cytometric analysis: In addition to the characteristic leukocytic dysfunctions, fluorescence cytometric analysis of cellular granularity and surface molecules offer useful diagnostic information.

Imaging Studies

• Oral radiographs reveal extensive loss of alveolar bone, leading to tooth exfoliation in most cases.
• CT scans and MRIs demonstrate diffuse brain and spinal cord atrophy.

Other Tests

• Light and electron microscopic examinations of biopsy specimens of periodontal tissues reveal massive bacterial invasion of epithelial tissue, epithelial cells, and connective tissue.
• Ultrastructural observations of periodontal polymorphonuclear leukocytes reveal defective granulation, with abnormal granules not discharging their lysosomal content against the engulfed bacteria. Viable dividing bacteria are found in the cytoplasm.
• Prenatal diagnosis can be made by examination of hair from fetal scalp biopsy specimens and of leukocytes from fetal blood samples.

Histologic Findings

A skin biopsy specimen usually appears entirely normal but may show melanin macroglobules and perhaps sparse dermal melanin. Ultrastructural examination reveals large abnormal type stage IV melanosomes that are transferred to keratinocytes with difficulty and are degraded rapidly.

Treatment

Medical Care

Allogenic bone marrow transplantation (BMT) from an HLA-matched sibling is the therapy of choice and should performed early. If no matched family donor is available, an unrelated donor or a placental blood graft is a good alternative.¹⁵ BMT alleviates the immune problems and the accelerated phase, but it does not inhibit the development of neurologic disorders, which become increasingly worse with age. BMT corrects the immunologic status but does not affect pigment dilution. Without BMT, children with Chédiak-Higashi syndrome usually die before age 10 years.

• Administration of acyclovir; high-dose intravenous gamma globulin; and microtubulytic drugs, such as vincristine, vinblastine, and colchicine, is effective in the management of the accelerated phase.
• Ascorbic acid corrects the microtubular defects in vitro but has no clinically ameliorative effect.
• Some authors have demonstrated that interferon partially restores the function of natural killer cells.
• Trottestam et al report that hemophagocytic lymphohistiocytosis can be effective as a first-line treatment and may induce remission.¹⁶

Surgical Care

Debridement and drainage of deep abscesses may be performed.

Consultations

A physician who specializes in hematologic disorders should be involved in the care of these patients.

• Neurologist: Neurologic involvement, such as loss of deep tendon reflexes due to peripheral neuropathy, cerebellar ataxia, intellectual impairment, nystagmus, and the Babinski sign, is often observed in the course of Chédiak-Higashi syndrome.
• Hematologist: The accelerated phase resembles lymphoma. Allogenic bone marrow or stem cell transplantation is the treatment of choice to correct the hematologic manifestation of the disease.
• Ophthalmologist: Ophthalmologists should be aware that progressive visual loss and the constriction of visual field can occur in patients with Chediak-Higashi syndrome as they grow older.¹⁷

Activity

Some activity limitations are advised because of the bruising problem and the bleeding tendency.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antiviral agents

These agents inhibit DNA synthesis and viral replication. Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase.
Use as suggested and dosing below is not for antiviral properties but for cellular antimitotic activity at high doses for the accelerated phase.

Acyclovir (Zovirax)

Inhibits activity of both HSV-1 and HSV-2. Has affinity for viral thymidine kinase and once phosphorylated causes DNA chain termination when acted on by DNA polymerase.
Use as suggested and dosing below is not for antiviral properties but for cellular antimitotic activity at high doses for the accelerated phase.

Dosing

Adult

30 mg/kg IV tid for 2-3 wk

Pediatric

10 mg/kg IV tid for 2-3 wk

Interactions

May decrease phenytoin plasma concentrations, which may cause increase in seizure activity; coadministration with meperidine may increase risk of CNS stimulation causing increase risk of seizures; may decrease valproic acid plasma concentrations, causing increased risk in seizure activity; concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity; use of acyclovir together with varicella vaccine usually not recommended (may decrease efficacy of varicella vaccine)

Contraindications

Documented hypersensitivity to drug or related products

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure or when using nephrotoxic drugs; maintain adequate hydration; thrombotic thrombocytopenic purpura/hemolytic uremic syndrome may occur (some cases resulting in death); caution in geriatric patients (higher plasma levels due to age-related decline in renal function)

Immune modulators

These agents inhibit key steps in immune reactions.

Immune globulin intravenous (Sandoglobulin, Gammagard, Gamimune, Gammar-P)

Neutralize circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).

Dosing

Adult

Primary immune deficiency disorder:
100-200 mg/kg (Vivaglobin) SC qwk; adjust dose and dosing interval to achieve desired clinical response and serum IgG levels
100-600 mg/kg IV qmo, may be given more frequently as indicated; not to exceed 1 g/kg/dose
0.66 mL/kg (at least 100 mg/kg) IM q3-4wk, double dose given at onset of therapy; some patients may require more frequent injections

Pediatric

Administer as in adults

Interactions

Increases toxicity of live virus vaccine (MMR); do not administer within 3 mo after therapy with IM immune globulin and 6 mo after therapy with IV immune globulin)

Contraindications

Documented hypersensitivity; IgA deficiency; anti–IgE/IgG antibodies

Precautions

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

Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia; blood pressure decline; following IV administration; related to infusion rate; adverse effects include acute respiratory distress syndrome, aseptic meningitis, hemolytic anemia, hepatitis, and hypokalemic nephropathy; myocardial infarction; pulmonary edema

Interferon alfa-2a and -2b (Roferon-A, Intron A)

Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.

Dosing

Adult

9 mcg SC 3 times/wk for 24 wk

Pediatric

Not established

Interactions

Theophylline may increase interferon alpha toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity of interferon alpha

Contraindications

Documented hypersensitivity

Precautions

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 brain metastases, cardiac disease, autoimmune disease, immunosuppressed transplant patients, severe hepatic or renal insufficiencies, seizure disorders, depression, multiple sclerosis, or compromised CNS; may cause spastic diplegia in children; may cause GI tract hemorrhage, leukopenia, hyperglycemia, and elevate hepatic transaminase levels; may potentiate risk of renal failure

Antineoplastic agents

These agents inhibit cell growth and proliferation. Useful in the accelerated phase of the disease.

Vincristine (Vincasar PFS, Oncovin)

Mechanism of action is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production. Reduce dose by 50% if direct bilirubin level > 3 mg/100 mL.

Dosing

Adult

1.4 mg/m²/wk IV

Pediatric

<10 kg: 0.05 mg/kg/wk IV initial
>10 kg: Administer as in adults; not to exceed 2 mg

Interactions

Acute pulmonary reaction may occur when taken concurrently with mitomycin-C; asparaginase, CYP450 3A4 inhibitors (eg, itraconazole, quinupristin/dalfopristin, sertraline, ritonavir), GM-CSF (eg, sargramostim, filgrastim), or nifedipine increase toxicity; CYP450 3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin) may decrease effects; administer asparaginase after vincristine rather than before or concurrently to avoid increased risk of toxicity; vaccination with live vaccine in patient immunocompromised by chemotherapeutic agent has resulted in severe and fatal infections; decreases effect of digoxin; concomitant administration of zidovudine with drugs like vincristine which are cytotoxic or suppress bone marrow function may increase the risk of hematologic toxicity; valspodar is capable of increasing plasma levels of vincristine and enhancing its toxicity in cancer patients

Contraindications

Documented hypersensitivity; demyelinating form of Charcot-Marie-Tooth syndrome; IT administration may cause death

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with severe cardiopulmonary or hepatic impairment, leukopenia, and patients with preexisting neuromuscular disease; may cause acute uric acid nephropathy, hypertension, hypotension, and leukopenia; vincristine is a vesicant (if extravasation occurs, treatment includes cold compresses and infiltration of the area with 8.4% sodium bicarbonate); syndrome of inappropriate antidiuretic hormone described after long-term therapy

Vinblastine (Alkaban-AQ, Velban)

Inhibits microtubule formation, which, in turn, disrupts the formation of the mitotic spindle, causing cell proliferation to arrest at metaphase. Use hematologic parameters as a guide. If direct bilirubin level >3, then reduce dose by 50%.
Local injection of hyaluronidase and application of moderate heat to area of extravasation help disperse drug and are thought to minimize discomfort and possibility of cellulitis.

Dosing

Adult

First dose 3.7 mg/m² IV, second dose 5.5 mg/m² IV, third dose 7.4 mg/m² IV, fourth dose 9.25 mg/m² IV, fifth dose 11.1 mg/m² IV, at weekly intervals; increase dose weekly until maximum of 18.5 mg/m2; target WBC count reduction to 3000 cells/μ L

Pediatric

3-6 mg/m² initial; then administer as in adults

Interactions

Phenytoin plasma levels may be reduced when administered concomitantly with vinblastine; with mitomycin, the toxicity of vinblastine may significantly increase
Concomitant administration of zidovudine with drugs like vinblastine, which are cytotoxic or suppress bone marrow function, may increase risk of hematologic toxicity

Contraindications

Documented hypersensitivity; bacterial infections (especially if granulocytopenic) and bone marrow suppression

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with ulcers of the skin, cachexia, impaired liver function, and neurotoxicity; when patient is receiving mitomycin C, monitor closely for shortness of breath and bronchospasm
Adverse effects include azoospermia, hypertension, hyperuricemia, leukopenia (dose-limiting), myelosuppression, and neurotoxicity; IV use only, intrathecal injection fatal
Leakage into surrounding tissue during intravenous administration may cause considerable irritation; avoid extravasation (if occurs, discontinue injection immediately and restart injection with remaining drug in another vein); malignant cell infiltration of bone marrow

Anti-inflammatory agents

Systemically interfere with events leading to inflammation.

Colchicine

Decreases leukocyte motility and phagocytosis in inflammatory responses.

Dosing

Adult

0.5-0.6 mg PO bid/tid

Pediatric

Not established

Interactions

Sympathomimetic agent toxicity and effect of CNS depressants significantly increased with colchicine
Concomitant administration of colchicine with clarithromycin, a potent inhibitor of CYP3A4 isoenzyme and p-glycoprotein transporter system, may result in significant increases in colchicine serum concentrations and serious pharmacodynamic consequences, including death
Concurrent use of cyclosporine and colchicine may result in gastrointestinal dysfunction, hepatonephropathy, and neuromyopathy due to combined toxicity; may decrease interferon alfa-2a effects

Contraindications

Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Risk of renal failure, hepatic failure, permanent hair loss, bone marrow suppression, numbness or tingling in hands and feet, disseminated intravascular coagulopathy, and decreased sperm count; dose-dependent GI upset is common
Administration of colchicine may lead to false-positive results when screening urine for red blood cells or hemoglobin

Follow-up

Further Outpatient Care

• Regular monitoring is needed.

Deterrence/Prevention

• Hygiene should be meticulous to avoid bacterial infections.
  • The skin should be washed 2 times a day with disinfectant soap to prevent skin infections.
  • Cutting the fingernails to a short length helps to reduce autoinoculation.
• Drugs that interfere with platelets (eg, acetylsalicylic acid–containing products) should be avoided.
• Excessive operative blood loss should be anticipated during the operation secondary to quantitative and qualitative defects in platelet function, and certain techniques (eg, epidural anesthesia, intramuscular injections) should be avoided.

Complications

• The skin is frequently involved, with pyodermas and deep abscesses.
• The thrombocytopenia and depletion of coagulation factors lead to petechiae, bruising, and gingival bleeding.
• Renal function may be impaired because of the involvement of the renal tubular epithelium.
• The progressive visual loss and the constriction of visual field can occur

Prognosis

• This syndrome usually leads to early death from infection or, less commonly, hemorrhage. Intractable respiratory and cutaneous infections usually prove fatal before a child with Chédiak-Higashi syndrome reaches age 10 years. Longer survival is possible, but the lymph nodes, spleen, and liver become enlarged and a malignant lymphoma develops. A few patients have survived to age 20 years.
• Price et al report a patient with Chédiak-Higashi syndrome whose pregnancy, labor, and delivery were not affected. The infant and placenta were normal.¹⁸

References

1. Demirkiran O, Utku T, Urkmez S, Dikmen Y. Chediak-Higashi syndrome in the intensive care unit. Paediatr Anaesth. Aug 2004;14(8):685-8. [Medline].

2. Jayaranee S, Menaka N. Chediak-Higashi syndrome: a case report. Malays J Pathol. Jun 2004;26(1):53-7. [Medline].

3. Kanjanapongkul S. Chediak-Higashi syndrome: report of a case with uncommon presentation and review literature. J Med Assoc Thai. Apr 2006;89(4):541-4. [Medline].

4. Barbosa MD, Barrat FJ, Tchernev VT, et al. Identification of mutations in two major mRNA isoforms of the Chediak-Higashi syndrome gene in human and mouse. Hum Mol Genet. Jul 1997;6(7):1091-8. [Medline].

5. Certain S, Barrat F, Pastural E, et al. Protein truncation test of LYST reveals heterogenous mutations in patients with Chediak-Higashi syndrome. Blood. Feb 1 2000;95(3):979-83. [Medline].

6. Mottonen M, Lanning M, Baumann P, Saarinen-Pihkala UM. Chediak-Higashi syndrome: four cases from Northern Finland. Acta Paediatr. Sep 2003;92(9):1047-51. [Medline].

7. Al-Khenaizan S. Hyperpigmentation in Chediak-Higashi syndrome. J Am Acad Dermatol. Nov 2003;49(5 Suppl):S244-6. [Medline].

8. Delcourt-Debruyne EM, Boutigny HR, Hildebrand HF. Features of severe periodontal disease in a teenager with Chédiak-Higashi syndrome. J Periodontol. May 2000;71(5):816-24. [Medline].

9. Bailleul-Forestier I, Monod-Broca J, Benkerrou M, Mora F, Picard B. Generalized periodontitis associated with Chediak-Higashi syndrome. J Periodontol. Jul 2008;79(7):1263-70. [Medline].

10. Kaplan J, De Domenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol. Jan 2008;15(1):22-9. [Medline].

11. Westbroek W, Adams D, Huizing M, ei al. Cellular defects in Chediak-Higashi syndrome correlate with the molecular genotype and clinical phenotype. J Invest Dermatol. Nov 2007;127(11):2674-7. [Medline].

12. Premalata C, Devi L, Madhumathi DS, Appaji L. Chediak-Higashi syndrome masquerading as acute leukemia: the significance of lymphocyte inclusions. J Clin Oncol. Jul 20 2006;24(21):3505-7. [Medline].

13. Valente NY, Machado MC, Boggio P, et al. Polarized light microscopy of hair shafts aids in the differential diagnosis of Chediak-Higashi and Griscelli-Prunieras syndromes. Clinics (Sao Paulo). Aug 2006;61(4):327-32. [Medline].

14. Wolf J, Jacobi C, Breer H, Grau A. [Chediak-Higashi syndrome]. Nervenarzt. Feb 2006;77(2):148, 150-2, 155-7. [Medline].

15. Liang JS, Lu MY, Tsai MJ, Lin DT, Lin KH. Bone marrow transplantation from an HLA-matched unrelated donor for treatment of Chediak-Higashi syndrome. J Formos Med Assoc. Jun 2000;99(6):499-502. [Medline].

16. Trottestam H, Beutel K, Meeths M, et al. Treatment of the X-linked lymphoproliferative, Griscelli and Chediak-Higashi syndromes by HLH directed therapy. Pediatr Blood Cancer. Feb 2009;52(2):268-72. [Medline].

17. Sayanagi K, Fujikado T, Onodera T, Tano Y. Chediak-Higashi syndrome with progressive visual loss. Jpn J Ophthalmol. May-Jun 2003;47(3):304-6. [Medline].

18. Price FV, Legro RS, Watt-Morse M, Kaplan SS. Chediak-Higashi syndrome in pregnancy. Obstet Gynecol. May 1992;79(5 (Pt 2)):804-6. [Medline].

19. Aslan Y, Erduran E, Gedik Y, Mocan H, Yildiran A. The role of high dose methylprednisolone and splenectomy in the accelerated phase of Chediak-Higashi syndrome. Acta Haematol. 1996;96(2):105-7. [Medline].

20. Baldus M, Zunftmeister V, Geibel-Werle G, et al. Chediak-Higashi-Steinbrinck syndrome (CHS) in a 27-year-old woman--effects of G-CSF treatment. Ann Hematol. Jul 1999;78(7):321-7. [Medline].

21. Barton LM, Roberts P, Trantou V, Haworth C, Kelsey H, Blamires T. Chediak-Higashi syndrome. Br J Haematol. Apr 2004;125(1):2. [Medline].

22. Braun-Falco O, Plewig G, Wolff HH, Burgdorf WHC. Chediak-Higashi syndrome. In: Dermatology. 2^nd ed. Berlin, Germany: Springer-Verlag; 2000:1029.

23. Carnide EM, Jacob CM, Pastorino AC, Bellinati-Pires R, Costa MB, Grumach AS. Chediak-Higashi syndrome: presentation of seven cases. Sao Paulo Med J. Nov-Dec 1998;116(6):1873-8. [Medline].

24. Hauser RA, Friedlander J, Baker MJ, Thomas J, Zuckerman KS. Adult Chediak-Higashi parkinsonian syndrome with dystonia. Mov Disord. Jul 2000;15(4):705-8. [Medline].

25. Introne W, Boissy RE, Gahl WA. Clinical, molecular, and cell biological aspects of Chediak-Higashi syndrome. Mol Genet Metab. Oct 1999;68(2):283-303. [Medline].

26. Kapoor A, Munjal S, Arya R. Chediak-Higashi syndrome--a case report. Indian J Pathol Microbiol. Jul 2000;43(3):373-5. [Medline].

27. Lazarchick J, McRae B. Chediak-Higashi syndrome. Blood. Jun 1 2005;105(11):4162. [Medline].

28. Ward DM, Shiflett SL, Huynh D, Vaughn MB, Prestwich G, Kaplan J. Use of expression constructs to dissect the functional domains of the CHS/beige protein: identification of multiple phenotypes. Traffic. Jun 2003;4(6):403-15. [Medline].

29. Ward DM, Shiflett SL, Kaplan J. Chediak-Higashi syndrome: a clinical and molecular view of a rare lysosomal storage disorder. Curr Mol Med. Aug 2002;2(5):469-77. [Medline].

Keywords

Chédiak-Higashi syndrome, Bequez Cesar syndrome, Chédiak-Steinbrinck-Higashi syndrome, CHS, immunodeficiency disorder, abnormal intracellular protein transport, LYST gene, CHS1 gene

Contributor Information and Disclosures

Author

Roman Janusz Nowicki, MD, PhD, Associate Professor, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland
Roman Janusz Nowicki, MD, PhD is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, and International Society for Human and Animal Mycology
Disclosure: Nothing to disclose.

Medical Editor

Jacek C Szepietowski, MD, PhD, Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
Disclosure: Stiefel Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

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