Cartilage-Hair Hypoplasia Medication

Updated: Aug 06, 2019
  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Medication Summary

IVIG replacement therapy

The overall consensus among clinical immunologists is that intravenous immunoglobulin (IVIG) administered at a dose of 400–600 mg/kg/mo or a dose that maintains trough serum immunoglobulin (Ig)G levels of more than 500 mg/dL is desirable. [45, 46] Patients with X-linked agammaglobulinemia and meningoencephalitis require much higher doses (1 g/kg) and, perhaps, intrathecal therapy. The measurement of preinfusion (trough) serum IgG levels every 3 months until a steady state is achieved and then every 6 months if the patient is stable may be helpful in adjusting the dose of IVIG to achieve adequate serum levels. For persons who have a high catabolism of infused IgG, more frequent infusions (eg, every 2–3 wk) of smaller doses may maintain the serum level within the reference range. The rate of elimination of IgG may be higher during a period of active infection; measuring serum IgG levels and adjusting to higher dosages or shorter dosing intervals may be required.

For replacement therapy in patients with primary immune deficiency, all brands of IVIG are probably equivalent, although viral inactivation processes differ (eg, solvent detergent vs pasteurization and liquid vs lyophilized). The choice of brand depends on the hospital or home care formulary and local availability and cost. The dose, manufacturer, and lot number should be recorded for each infusion to review for adverse events or other consequences. Recording all adverse effects that occur during the infusion is crucial. Monitoring liver and renal function test results periodically, approximately 3–4 times annually, is also recommended.

The US Food and Drug Administration (FDA) recommends that, in patients at risk for renal failure (eg, preexisting renal insufficiency, diabetes, volume depletion, sepsis, paraproteinemia, age >65 y, use of nephrotoxic drugs), recommended doses should not be exceeded, and infusion rates and concentrations should be administered at the minimum levels that are practicable.

Initial treatment should be administered under the close supervision of experienced personnel. The risk of adverse reactions in initial treatments is high, especially in patients with infections and in those who form immune complexes. In patients with active infection, infusion rates may need to be slower and the dose may need to be halved (ie, 200–300 mg/kg), with the remaining dose administered the next day to achieve a full dose. Treatment should not be discontinued. After achieving serum IgG levels within reference range, adverse reactions are uncommon, unless patients have active infections.

Adverse affects associated with the new generation of IVIG products have been greatly reduced and include tachycardia, chest tightness, back pain, arthralgia, myalgia, hypertension or hypotension, headache, pruritus, rash, and low-grade fever. More serious reactions include dyspnea, nausea, vomiting, circulatory collapse, and loss of consciousness. Patients with more profound immunodeficiency or patients with active infections have more severe reactions.

Anticomplementary activity of IgG aggregates in the IVIG, and the formation of immune complexes are thought to be related to the adverse reactions. Another cause is the formation of oligomeric or polymeric IgG complexes that interact with Fc receptors and trigger the release of inflammatory mediators. Most adverse reactions are rate related. Slowing the infusion rate or discontinuing therapy until symptoms subside may diminish the reaction. Pretreatment with ibuprofen (5–10 mg/kg every 6–8 h), acetaminophen (15 mg/kg/dose), diphenhydramine (1 mg/kg/dose), hydrocortisone (6 mg/kg/dose, maximum 100 mg), or a combination 1 hour before the infusion may prevent adverse reactions. In some patients with a history of severe adverse effects, analgesic and antihistamine administration may be repeated.

Acute renal failure is a rare but significant complication of IVIG treatment. Reports suggest that IVIG products using sucrose as a stabilizer may be associated with a greater risk for this renal complication. Acute tubular necrosis, vacuolar degeneration, and osmotic nephrosis suggest osmotic injury to the proximal renal tubules. The infusion rate for sucrose-containing IVIG should not exceed 3 mg sucrose per kg/min. Risk factors for this adverse reaction include preexisting renal insufficiency, diabetes mellitus, dehydration, age older than 65 years, sepsis, paraproteinemia, and concomitant use of nephrotoxic agents. For patients at an increased risk, monitoring BUN and creatinine levels before starting the treatment and prior to each infusion is necessary. If renal function deteriorates, the product should be discontinued.

IgE antibodies to IgA have been reported to cause severe transfusion reactions in patients with IgA deficiency. True anaphylaxis has been reported in patients with selective IgA deficiency and common variable immunodeficiency who developed IgE antibodies to IgA after treatment with immunoglobulin. However, this is rare. In addition, this is not a problem in patients with X-linked agammaglobulinemia (Bruton disease) or severe combined immunodeficiency (SCID). Exercise caution in patients with IgA deficiency (< 7 mg/dL) who require IVIG administration because of IgG subclass deficiencies. IVIG preparations with low concentrations of contaminating IgA are advised (see the Table below).

Table 1. Immunoglobulin, Intravenous [47, 48, 49, 50] (Open Table in a new window)

Brand (Manufacturer)

Manufacturing Process


Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs])

Parenteral Form and Final Concentrations

IgA Content (mcg/mL)

Carimune NF

(CSL Behring)

Kistler-Nitschmann fractionation; pH 4, nanofiltration


6% solution: 10% sucrose, < 20 mg NaCl/g protein

Lyophilized powder 3%, 6%, 9%, 12%



(Grifols USA)

Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization


Sucrose free, contains 5% D-sorbitol

Liquid 5%

< 50

Gammagard Liquid 10%

(Baxter Bioscience)

Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation


0.25M glycine

Ready-for-use liquid 10%



(Talecris Biotherapeutics)

Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation


Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycine

Liquid 10%



(Bio Products)

Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation


Contains sorbitol (40 mg/mL); do not administer if fructose intolerant

Ready-for-use solution 5%

< 10

Iveegam EN

(Baxter Bioscience)

Cohn-Oncley fraction II/III; ultrafiltration; pasteurization


5% solution: 5% glucose, 0.3% NaCl

Lyophilized powder 5%

< 10

Polygam S/D

Gammagard S/D

(Baxter Bioscience for the American Red Cross)

Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated


5% solution: 0.3% albumin, 2.25% glycine, 2% glucose

Lyophilized powder 5%, 10%

< 1.6 (5% solution)


(Octapharma USA)

Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization


10% maltose

Liquid 5%



(Swiss Red Cross for the American Red Cross)

Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration


Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl

Lyophilized powder 3%, 6%, 9%, 12%


Privigen Liquid 10%

(CSL Behring)

Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration


L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose)

Ready-for-use liquid 10%

< 25

Treat infections with appropriate antimicrobial agents. Treat varicella infections with acyclovir. Prophylactic acyclovir is probably not beneficial in the prevention of varicella. Live viral vaccines should be avoided in these patients. The recently developed attenuated varicella vaccine may help reduce varicella infection in patients with cartilage-hair hypoplasia; however, no studies have confirmed this, and patients with cartilage-hair hypoplasia may develop vaccine-related varicella infection.


Antiviral Agents

Class Summary

Nucleoside analogs are initially phosphorylated by viral thymidine kinase (TK) to eventually form a nucleoside triphosphate.

Acyclovir (Zovirax)

Synthetic purine nucleoside analogue that inhibits herpes virus replication. Herpes virus TK, but not host cell TK, uses acyclovir as a purine nucleoside, converting it into acyclovir monophosphate, a nucleotide analogue. Guanylate kinase converts the monophosphate form into diphosphate and triphosphate analogues that inhibit viral DNA replication.

Valacyclovir (Valtrex)

Valacyclovir is metabolized to acyclovir and L-valine with better oral absorption than acyclovir.



Class Summary

Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components, which act as antigens. Vaccine administration stimulates the production of antibodies with specific protective properties.

Varicella virus vaccine, live attenuated (Varivax)

Attenuated live varicella virus prepared from the Oka/Merck strain. It is propagated in human diploid cell cultures (MRC-5). Each 0.5-mL dose (when reconstituted) contains 1350 PFU of varicella, sucrose, and gelatin; residual components of MRC-5 DNA and protein; plus trace quantities of neomycin and fetal bovine serum. Indicated for vaccination against varicella in individuals >1 y.