eMedicine Specialties > Neurology > Pediatric Neurology
Xeroderma Pigmentosum: Treatment & Medication
Updated: Jan 8, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Skin hypersensitivity and skin cancer should be treated by a dermatologist.
- Neurologic care is mostly supportive. Seizures can be treated like other complex partial seizures with secondary generalization. Spasticity is usually mild. If it interferes with mobility, baclofen or botulinum toxin (BOTOX®) injection may be beneficial.
Consultations
Every patient with xeroderma pigmentosum needs to be monitored regularly by a dermatologist and ophthalmologist. Consultation with a geneticist may help to differentiate xeroderma pigmentosum from other related conditions, such as Cockayne syndrome and progeria.
Activity
Patients must avoid the sun to protect their skin. If sun exposure cannot be entirely avoided, patients should wear long sleeves, use sunscreen with SPF 50, and wear dark glasses. Some families reverse their day/night cycle to eliminate sun exposure entirely.Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Anticonvulsants
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
Carbamazepine (Tegretol, Carbatrol, Epitol)
Treats complex partial seizures. Appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Major mechanism of action is to reduce sustained high-frequency repetitive neural firing.
Adult
200 mg PO bid (100 mg qid of susp); increase at weekly intervals by <200 mg/d using tid/qid regimen (bid with extended release) until best response obtained; not to exceed 1600 mg/d
Pediatric
<6 years: 10-20 mg/kg/d PO bid/tid (qid with susp); increase weekly to achieve optimal clinical response administered tid/qid
6-12 years: 100 mg bid PO (50 mg qid of susp); increase at weekly intervals gradually by adding 100 mg/d using tid/qid regimen (bid with extended release) until best response obtained; dosage generally should not exceed 1000 mg/d
>12 years: Administer as in adults; not to exceed 1000 mg/d in children 12-15 years or 1200 mg/d in >15 years
Do not coadminister with MAOIs
Danazol within last 30 d may increase serum levels significantly (avoid whenever possible); cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels)
Documented hypersensitivity; history of bone marrow depression; MAOIs within last 14 d
Pregnancy
D - Unsafe in pregnancy
Precautions
Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBC count and serum iron level prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness
Phenytoin (Dilantin)
May act in motor cortex where may inhibit spread of seizure activity. Activity of brain stem centers responsible for tonic phase of grand mal seizures also may be inhibited.
Dose should be individualized. Administer larger dose before retiring if dose cannot be divided equally. Phosphorylated formulation, fosphenytoin, available for parenteral use and may be given IM or IV.
Adult
Initial dose: 100 mg (125 mg susp) IV/PO tid
Maintenance dose: 300-400 mg/d PO/IV divided tid, or qd/bid if using extended release; increase to 600 mg/d (625 mg/d susp) may be necessary; do not exceed 1500 mg/24h
Rate of infusion must not exceed 50 mg/min to avoid hypotension and arrhythmias
Pediatric
Initial dose: 5 mg/kg/d PO/IV divided bid/tid
Maintenance dose: 4-8 mg/kg PO/IV divided bid/tid
>6 years: May require minimum adult dose (300 mg/d); not to exceed 300 mg/d
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity
Barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid
Documented hypersensitivity; sino-atrial block; second- or third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
Pregnancy
D - Unsafe in pregnancy
Precautions
Rapid IV infusion may result in death from cardiac arrest, marked by QRS widening
Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash appears and do not resume if rash is exfoliative, bullous, or purpuric; caution in acute intermittent porphyria and diabetes (may elevate blood sugars); discontinue use if hepatic dysfunction occurs
Valproic acid (Depakote, Depakene, Depacon)
Chemically unrelated to other drugs that treat seizure disorders. Although mechanism of action not established, activity may be related to increased brain levels of GABA, or enhanced GABA action.
Also may potentiate postsynaptic GABA responses, affect potassium channel, or have direct membrane-stabilizing effect.
For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% every 2 wk. This reduction may start at initiation of therapy or be delayed by 1-2 wk if concern that seizures may occur with reduction. Monitor patients closely during this period for increased seizure frequency.
As adjunctive therapy, divalproex sodium may be added to patient's regimen at 10-15 mg/kg/d. May increase by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response achieved at daily doses <60 mg/kg/d.
Adult
Monotherapy: 10-15 mg/kg/d PO in 1-3 divided doses and increase by 5-10 mg/kg/wk; not to exceed 60 mg/kg/d until seizures controlled or adverse effects prevent further increases
If daily dose >250 mg, give in divided doses
Pediatric
Administer as in adults
Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce levels significantly; in children, salicylates decrease protein binding and metabolism; may result in variable changes of carbamazepine concentrations with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels while either may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-seropositive patients
Documented hypersensitivity; hepatic disease/dysfunction
Pregnancy
D - Unsafe in pregnancy
Precautions
Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet count and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or hemostasis/coagulation disorder occurs; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness
More on Xeroderma Pigmentosum |
| Overview: Xeroderma Pigmentosum |
| Differential Diagnoses & Workup: Xeroderma Pigmentosum |
 Treatment & Medication: Xeroderma Pigmentosum |
| Follow-up: Xeroderma Pigmentosum |
| Multimedia: Xeroderma Pigmentosum |
| References |
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References
Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. Feb 1987;123(2):241-50. [Medline].
Mimaki T, Itoh N, Abe J, et al. Neurological manifestations in xeroderma pigmentosum. Ann Neurol. Jul 1986;20(1):70-5. [Medline].
Anttinen A, Koulu L, Nikoskelainen E, Portin R, Kurki T, Erkinjuntti M, et al. Neurological symptoms and natural course of xeroderma pigmentosum. Brain. Aug 2008;131:1979-89. [Medline].
Jaspers NG, Raams A, Silengo MC, Wijgers N, Niedernhofer LJ, Robinson AR, et al. First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure. Am J Hum Genet. Mar 2007;80(3):457-66. [Medline].
Cleaver JE. Defective repair replication of DNA in xeroderma pigmentosum. Nature. May 18 1968;218(5142):652-6. [Medline].
De Sanctinis C, Cacchione A. L'idiozia xerodermica. Riv Sepr Freniatr. 1932;56:269-292.
Hakamada S, Watanabe K, Sobue G, et al. Xeroderma pigmentosum: neurological, neurophysiological and morphological studies. Eur Neurol. 1982;21(2):69-76. [Medline].
Hayashi M, Araki S, Kohyama J, et al. Oxidative nucleotide damage and superoxide dismutase expression in the brains of xeroderma pigmentosum group A and Cockayne syndrome. Brain Dev. Jan 2005;27(1):34-8. [Medline].
Johnson RT, Squires S. The XPD complementation group. Insights into xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy. Mutat Res. Mar 1992;273(2):97-118. [Medline].
Kohyama J, Furushima W, Sugawara Y, et al. Convulsive episodes in patients with group A xeroderma pigmentosum. Acta Neurol Scand. Oct 2005;112(4):265-9. [Medline].
Lehmann AR. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie. Nov 2003;85(11):1101-11. [Medline].
Mimaki T, Tagawa T, Tanaka J, et al. EEG and CT abnormalities in xeroderma pigmentosum. Acta Neurol Scand. Aug 1989;80(2):136-41. [Medline].
Moriwaki S, Nishigori C, Imamura S, et al. A case of xeroderma pigmentosum complementation group F with neurological abnormalities. Br J Dermatol. Jan 1993;128(1):91-4. [Medline].
Nance MA, Berry SA. Cockayne syndrome: review of 140 cases. Am J Med Genet. Jan 1 1992;42(1):68-84. [Medline].
Rapin I, Weidenheim K, Lindenbaum Y, et al. Cockayne syndrome in adults: review with clinical and pathologic study of a new case. J Child Neurol. Nov 2006;21(11):991-1006. [Medline].
Robbins JH, Brumback RA, Mendiones M, et al. Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form. Brain. Jun 1991;114 ( Pt 3):1335-61. [Medline].
Robbins JH, Brumback RA, Moshell AN. Clinically asymptomatic xeroderma pigmentosum neurological disease in an adult: evidence for a neurodegeneration in later life caused by defective DNA repair. Eur Neurol. 1993;33(3):188-90. [Medline].
Robbins JH, Kraemer KH, Lutzner MA, et al. Xeroderma pigmentosum. An inherited diseases with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair. Ann Intern Med. Feb 1974;80(2):221-48. [Medline].
Roytta M, Anttinen A. Xeroderma pigmentosum with neurological abnormalities. A clinical and neuropathological study. Acta Neurol Scand. Feb 1986;73(2):191-9. [Medline].
Weeda G, Ma LB, van Ham RC, et al. Structure and expression of the human XPBC/ERCC-3 gene involved in DNA repair disorders xeroderma pigmentosum and Cockayne's syndrome. Nucleic Acids Res. Nov 25 1991;19(22):6301-8. [Medline].
Weeda G, van Ham RC, Vermeulen W, et al. A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome. Cell. Aug 24 1990;62(4):777-91. [Medline].
Further Reading
Keywords
XP, De Sanctis-Cacchione syndrome, sensitivity to ultraviolet light, light sensitivity, skin cancer, abnormal skin pigmentation, Cockayne syndrome, CS
