eMedicine Specialties > Dermatology > Diseases of Pigmentation
Griscelli Syndrome: Treatment & Medication
Updated: Feb 1, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Medical treatment of patients with GS is difficult.
- For patients with defects in RAB27A, antibiotics and antiviral agents are used with mixed effects. Similarly, medications may not control the neurologic symptoms of the disease.
- In GS related to MYO5A mutations, no specific treatment exists because the defect is in the brain rather than in the blood cells as in cases caused by the RAB27A mutation. The severe neurologic impairment and retarded psychomotor development do not improve with time.
- Only bone marrow transplantation offers a possibility of extended survival. In preparation for transplantation, particularly in patients with GS caused by a mutation in RAB27A, various immunosuppressive regimens have been used to attenuate HS (accelerated phase).
- Mehdizadeh and Zamani28 noted a 10-year-old boy with GS and macrophage activation syndrome, which was controlled with immunosuppressive therapy.
Surgical Care
Bone marrow transplantation is the most effective treatment of this condition. Bone marrow transplantation is the only possible cure for GS. Even a low number of donor cells in the patient's bone marrow can be sufficient to control symptoms of GS in cases caused by mutations in RAB27A.
Consultations
The specialists who are most often initially consulted for treatment of this condition are geneticists, hematologists, dermatologists, neurologists, and pediatricians. Once a diagnosis is made, such specialists should consider the need for chemotherapy in patients and how to proceed with bone marrow transplantation.
Diet
No special diet is recommended for patients with GS.
Activity
Because patients with GS can have severe neurologic and immunologic problems, their activities are usually limited.
- For patients, avoiding interactions that expose them to infections is important.
- Because patients with GS can have seizures that are difficult to control, they must be actively monitored.
Medication
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.
Immunosuppressants
These agents are 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.
Cyclosporine (Sandimmune, Neoral)
Used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.
Adult
This is not a disease of adults so these doses are provided based on the use of this drug in children
Initial PO dose: 14-18 mg/kg/d PO 4-12 h before organ transplantation
Maintenance PO dose: 5-15 mg/kg/d PO qd or divided bid
Initial IV dose: 5-6 mg/kg IV qd 4-12 h prior to organ transplantation
Maintenance IV dose: 2-10 mg/kg/d IV divided q8-12h
Pediatric
Initial PO dose: 5-15 mg/kg/d PO 4-12 h before organ transplantation
Maintenance PO dose: 5-15 mg/kg/d PO qd or divided bid
Initial IV dose: 5-6 mg/kg IV qd 4-12 h prior to organ transplantation
Maintenance IV dose: 2-10 mg/kg/d IV divided q8-12h
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin; methylprednisolone and cyclosporine mutually inhibit one another, resulting in increased plasma levels of each drug
Documented hypersensitivity
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
Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzyme levels; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO
Prednisone (Orasone, Meticorten, Sterapred, Deltasone)
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.
Adult
5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric
4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral, fungal, tubercular skin, or connective tissue infections; peptic ulcer disease; hepatic dysfunction; GI bleeding or ulceration
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Immunosuppressive antibodies
This agent is used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.
Antithymocyte globulins
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.
Adult
Pediatric
5-30 mg/kg/d IV infusion; these doses are determined empirically and have not been subject to trials
Very immunosuppressive when combined with other immunosuppressive agents
Documented hypersensitivity
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
The use of ATG, monoclonal anti-CD3 antibodies, or muromonab CD3 (OKT3) is hampered by numerous adverse effects, including a significant risk of overimmunosuppression
Antineoplastics
Used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.
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.
Adult
100 mg/m2 IV for 5 consecutive days
Pediatric
Not established
May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Bleeding and severe myelosuppression may occur
Antimetabolites
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.
Cytarabine (Cytosar-U)
Used as part of an immunosuppressive regimen.
Adult
Not established
Pediatric
100-200 mg/m2/d IV for 5-10 d or qd until remission
Alternatively, may administer the following dosages for 5-10 d or qd until remission:
<1 year: 20 mg IV
1-2 years: 30 mg IV
2-3 years: 50 mg IV
>3 years: 70 mg IV
Decreases effects of gentamicin and flucytosine; other alkylating agents and radiation increase toxicity
Documented hypersensitivity
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
If significant increase in bone marrow suppression, reduce number of treatment days; patients with hepatic or renal insufficiencies are at higher risk for CNS toxicity after a high dose (reduce dose)
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.
Adult
Not established
Pediatric
Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, can increase MTX plasma levels; may decrease phenytoin plasma levels; may increase thiopurine plasma levels
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant decrease in blood counts occur; fatal reactions reported when administered concurrently with NSAIDs
More on Griscelli Syndrome |
| Overview: Griscelli Syndrome |
| Differential Diagnoses & Workup: Griscelli Syndrome |
 Treatment & Medication: Griscelli Syndrome |
| Follow-up: Griscelli Syndrome |
| References |
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References
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Further Reading
Keywords
GS, MIM 214450, partial albinism with immunodeficiency, Griscelli-Prunieras syndrome, Griscelli-Prunieras variant, Griscelli's disease, Griscelli disease
