Griscelli Syndrome Medication

  • Author: Noah S Scheinfeld, MD, JD, FAAD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jul 18, 2011
 

Medication Summary

To suppress the accelerated phase (lymphohistiocytic infiltration of multiple organs, in particular the brain and the meninges) of disease, immunosuppressive therapy is used.

Chemotherapy (VP16) or, more recently, antithymocyte globulins (ATG) (10 mg/kg for 5 d) and cyclosporin A have achieved remissions, and the use of intrathecal methotrexate injections transiently help treat the neurocerebral involvement. However, chemotherapy is sometimes ineffective for the treatment of the primary disease and frequently fails to control relapses. Recurrent infections have been minimized with antibacterial and antiviral agents.

Other regimens that have resulted in the induction of remission have been obtained with the combination of high-dose systemic methylprednisolone and etoposide and intrathecal methotrexate, cytosine arabinoside, and prednisone, and with a regimen of ATGs, steroids, and cyclosporine, but these therapies are palliative rather than curative.

In one case, before a bone marrow transplant was performed, a child was given a preparative regimen consisting of busulfan, thiotepa, and fludarabine with good effect. In another case, when a patient experienced HS (accelerated phase) characterized by hemophagocytosis, the patient was treated with prednisolone, rabbit ATGs, and intrathecal methotrexate. Remission was maintained with cyclosporin A until HLA-compatible peripheral blood stem cell transplantation from the patient's mother was performed.

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Immunosuppressants

Class Summary

To suppress the accelerated phase (lymphohistiocytic infiltration of multiple organs, in particular the brain and the meninges) of disease, immunosuppressive therapy is used.

These agents include cyclic polypeptides that suppress some humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease, for a variety of organs. Prednisone is used to suppress T-cell and immune function.

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Cyclosporine (Sandimmune, Neoral)

 

Used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.

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Prednisone (Sterapred)

 

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.

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Immunosuppressive Antibodies

Class Summary

This agent is used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.

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Antithymocyte globulin equine

 

ATG is usually used as an antirejection medication. The mechanisms of action of polyclonal ATGs are still poorly understood, and the selection of doses used in different clinical applications (eg, prevention or treatment of acute rejection in organ allografts, treatment of graft-vs-host disease, conditioning for allogeneic stem cell transplantation) remains empirical. Low T-cell counts are usually achieved in peripheral blood during ATG treatment, but the extent of T-cell depletion in lymphoid tissues is unknown. T-cell depletion is achieved rapidly and primarily in peripheral lymphoid tissues at high ATG dosage.

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Antineoplastics

Class Summary

Used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.

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Etoposide (VePesid, Toposar)

 

Inhibits topoisomerase II and causes DNA strand breakage, resulting in cell proliferation to arrest in late S or early G2 portion of the cell cycle.

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Antimetabolites

Class Summary

Cytarabine is converted intracellularly to the active compound cytarabine-5'-triphosphate, which inhibits DNA polymerase. This inhibition, in turn, halts viral replication. Intrathecal methotrexate is an antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. Satisfactory response seen in 3-6 wk following administration. Adjust dose gradually to attain satisfactory response.

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Cytarabine (Cytosar-U)

 

Used as part of an immunosuppressive regimen.

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Intrathecal methotrexate (Folex PFS, Rheumatrex)

 

Used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease. Injected intrathecally to treat the neurologic complications. Patients are also given leucovorin to mitigate some effects of methotrexate.

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Optigenex Consulting fee Independent contractor

Coauthor(s)

Ann M Johnson, MD  Assistant Professor of Clinical Radiology, University of Pennsylvania School of Medicine; Director, Body MRI, Department of Radiology, Children's Hospital of Philadelphia

Ann M Johnson, MD is a member of the following medical societies: American Roentgen Ray Society, International Society for Magnetic Resonance in Medicine, Radiological Society of North America, Society for Pediatric Radiology, and Society of Computed Body Tomography and Magnetic Resonance

Disclosure: Nothing to disclose.

Specialty Editor Board

Julie C Harper, MD  Assistant Program Director, Assistant Professor, Department of Dermatology, University of Alabama at Birmingham

Julie C Harper, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Stiefel Honoraria Speaking and teaching; Allergan Honoraria Speaking and teaching; Intendis Honoraria Speaking and teaching; Coria Honoraria Speaking and teaching; Sanofi-Aventis Honoraria Speaking and teaching

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD  Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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