Chediak-Higashi Syndrome Treatment & Management

Updated: May 25, 2018
  • Author: Roman J Nowicki, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Treatment

Approach Considerations

Allogeneic transplantation from an HLA-matched sibling or from an unrelated donor or cord blood transplantation is the treatment of choice to correct the immunologic and hematologic manifestations of early-onset Chédiak-Higashi syndrome (CHS). Transplantation appears to be most successful when performed prior to the accelerated phase. Therefore, it would be of great value to differentiate patients who present with the childhood form of the disease from those who exhibit clinical phenotypes of adolescent and adult CHS, so as to prematurely enroll only the former ones in to a transplantation protocol. [11]

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Medical Care

 

Early treatment of children with Chédiak-Higashi syndrome (CHS) is of paramount importance.

Treatment of manifestations includes the following:

  • Initial chemoimmunotherapy followed by transition to continuation therapy for the accelerated phase
  • Allogenic hematopoietic stem cell transplantation (HSCT) as soon as possible to cure hematologic and immunologic defects
  • Platelet transfusions as needed for serious bleeding
  • Corrective lenses to improve visual acuity
  • Treatment by rehabilitation specialists for neurologic complications

The only treatment that cures the hematologic and immunologic defects is allogenic HSCT, but this therapy does not prevent the progressive neurological dysfunction frequently observed during long-term follow up. [5, 17] The current standard of care is HSCT as soon as the diagnosis is confirmed and the accelerated phase has either been ruled out or is in remission. The most favorable outcome is achieved when HSCT is performed prior to development of the accelerated phase. If signs of the accelerated phase are present, hemophagocytosis must be brought into clinical remission before HSCT can be performed. Guidelines for treatment of the accelerated phase are the same as those for familial hemophagocytic lymphocytic lymphohistiocytosis. Combination therapy consists of etoposide, dexamethasone, and cyclosporine A. Remission is achieved in 75% of individuals within 8 weeks; however, relapses are common and response to treatment declines over time. Once remission occurs, prompt HSCT is recommended.

Prevention of secondary complications includes the following:

  • Prompt aggressive use of antibiotics and antiviral agents for bacterial and viral illnesses
  • Routine immunizations
  • Intravenous desmopressin acetate prior to invasive procedures to help control bleeding

In patients with CHS and Epstein-Barr virus (EBV)–associated hemophagocytic lymphohistiocytosis (HLH), the addition of rituximab has been reported to be a valuable adjunct to therapy, although in contrast to normal EBV infection, in HLH patients, the virus is also present in T cells. Other treatment options include the anti-CD52 monoclonal antibody alemtuzumab as a second-line therapy for pretransplantation treatment of HLH refractory to etoposide-based treatments. [3]

A conditioning regimen generally includes a combination of etoposide, busulfan, and cyclophosphamide. [18]

The duration of antimicrobial therapy to treat common infections should ideally be two to three times longer than standard recommendations. Granulocyte colony-stimulating factor (G-CSF) can be used to improve or correct neutropenia and decrease infections.

Careful dental hygiene can minimize gingival bleeding, and treatment with desmopressin and/or antifibrinolytic agents is effective in preventing bleeding after dental extraction or minor surgery in patients with storage pool disease or mild bleeding disorders. Platelet transfusions are particularly indicated in cases of severe uncontrolled bleeding, when prior treatments have been unsuccessful and/or in the presence of, or anticipation of, excessive traumatic or surgical bleeding. [11]

A subset of CHS patients presenting with the adult form of the disorder have a muted pigmentary or hematologic presentation while their neurologic symptoms dominate the disease. Patients with this pattern of manifestations might benefit, at least in the short term, from L-dopa, selegiline, trihexyphenidyl, biperiden, or amantadine treatment. [11, 19]

Surveillance is as follows:

  • Yearly ophthalmologic examinations
  • For atypical or adolescent- or adult-onset CHS - Annual abdominal ultrasound examination for hepatosplenomegaly, complete blood cell (CBC) count for cytopenias, monitoring for liver dysfunction, and measurement of serum ferritin concentration and soluble interleukin 2 receptor [19]

Agents/circumstances to avoid include nonsteroidal anti-inflammatory drugs, which can exacerbate the bleeding tendency. [19]

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Surgical Care

Debridement and drainage of deep abscesses may be performed.

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Consultations

Increased awareness and the early identification of patients with the potentially lethal form of Chédiak-Higashi syndrome (CHS) convey unique therapeutic and prognostic implications that may improve outcomes. With a high degree of clinical suspicion, these patients should be immediately referred to a tertiary care center and treated by multidisciplinary teams including hematologists, pediatricians, dermatologists, biologists, neurologists, clinical immunologists, and social workers.

A neurologist should be consulted. 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 CHS.

Hematologist consultation is necessary because 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.

Ophthalmologists should be aware that progressive visual loss and the constriction of visual field can occur in patients with CHS as they grow older. [20]

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Activity

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

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Prevention

Chédiak-Higashi syndrome (CHS) patients may exhibit an increased bleeding tendency owing to platelet dysfunction caused by delta storage pool deficiency. Preventative measures include avoidance of drugs that interfere with platelet functions such as aspirin, other nonsteroidal anti-inflammatory agents, or serotonin reuptake inhibitors. Intramuscular injections are prohibited, but subcutaneous injections are authorized. [11]

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.

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.

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Long-Term Monitoring

Even though there are no general recommendations for clinical follow-up of patients with adult-onset Chédiak-Higashi syndrome (CHS), regular screening might include physical examination and/or abdominal ultrasound to monitor for hepatosplenomegaly, blood cell counts to evaluate cytopenias, biochemical tests to assess for signs of liver dysfunction, including serum ferritin levels, hypertriglyceridemia, and/or hypofibrinogenemia. [11, 19]

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