T-Cell Disorders Medication

Updated: Jun 12, 2020
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
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Medication

Medication Summary

Patients with partial T-cell deficiencies often have increased viral and bacterial respiratory infections. Conventional antibiotic therapy is administered for bacterial sinopulmonary infections; these infections are frequent but unlikely to be invasive unless the patient has undergone splenectomy. Individual patients may benefit from prophylaxis against infection by respiratory syncytial virus (RSV) or encapsulated bacteria by antibody replacement using intravenous immunoglobulin (IVIG) or specific anti-RSV antibodies.

By taking advantage of residual T-cell function, immunization against viral and bacterial agents may be efficacious. For example, the conjugated pneumococcal vaccine may induce antibody production that the unconjugated vaccine cannot. Most patients with partial T-cell disorders appear to have adequate immunoglobulin G (IgG) antibody responses to traditionally T-cell dependent antigens (eg, diphtheria, tetanus, pertussis, influenza, conjugated Haemophilus influenzae), although information regarding newer vaccines (eg, hepatitis viruses) is inadequate.

Down-regulation of autoimmune reactions requires therapy with corticosteroids and other immunosuppressive agents. These agents include monoclonal antibodies directed against cytokines (ie, tumor necrosis factor [TNF]-a in autoimmune enteropathy).

Replacement therapy with IVIG in patients with primary immune deficiencies

The overall consensus among clinical immunologists is that a dose of IVIG of 400-600 mg/kg/mo or a dose that maintains trough serum IgG levels at greater than 500 mg/dL is desirable. Patients with X-linked agammaglobulinemia with meningoencephalitis require much higher doses (1 g/kg) and, perhaps, intrathecal therapy. 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 in 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 doses or shorter intervals may be required.

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

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

The initial treatment should be administered under the close supervision of experienced personnel. The risk of adverse reactions in the initial treatments is high, especially in patients with infections and patients who form immune complexes. In patients with active infection, infusion rates may need to be slower and the dose 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.

With the new generation of IVIG products, adverse effects are reduced. Adverse effects include tachycardia, chest tightness, back pain, arthralgia, myalgia, hypertension or hypotension, headache, pruritus, rash, and low-grade fever. More serious reactions are 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 believed to be related to adverse reactions. The formation of oligomeric or polymeric IgG complexes that interact with Fc receptors and trigger the release of inflammatory mediators is another cause. 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), and/or hydrocortisone (6 mg/kg/dose, not to exceed 100 mg) 1 hour before the infusion may prevent adverse reactions. In some patients with a history of severe adverse effects, analgesics and antihistamines 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 are suggestive of osmotic injury to the proximal renal tubules. The infusion rate for sucrose-containing IVIG should not exceed 3 mg sucrose/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 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.

Immunoglobulin E (IgE) antibodies to immunoglobulin A (IgA) have been reported to cause severe transfusion reactions in patients with IgA deficiency. A few reports exist of true anaphylaxis in patients with selective IgA deficiency and common variable immunodeficiency that developed IgE antibodies to IgA after treatment with immunoglobulin. However, in actual experience, this response is very rare. In addition, this is not a problem for patients with X-linked agammaglobulinemia (Bruton disease) or severe combined immunodeficiency (SCID). Caution should be exercised in patients with IgA deficiency (< 7 mg/dL) who need IVIG because of IgG subclass deficiencies. IVIG preparations with very low concentrations of contaminating IgA are advised (see the Table below).

Table. Immune Globulin, Intravenous [29, 30, 31, 32] (Open Table in a new window)

Brand(Manufacturer)

Manufacturing Process

pH

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

6.4-6.8

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

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

720

Flebogamma

(Grifols USA)

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

5.1-6

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

4.6-5.1

0.25M glycine

Ready-for-use liquid 10%

37

Gamunex

(Talecris Biotherapeutics)

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

4-4.5

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

Liquid 10%

46

Iveegam EN

(Baxter Bioscience)

Cohn-Oncley fraction II/III; ultrafiltration; pasteurization

6.4-7.2

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

6.4-7.2

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

Lyophilized powder 5%, 10%

< 1.6 (5% solution)

Octagam

(Octapharma USA)

9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events

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

5.1-6

10% maltose

Liquid 5%

200

Panglobulin

(Swiss Red Cross for the American Red Cross)

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

6.6

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

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

720

Privigen Liquid 10%

(CSL Behring)

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

4.6-5

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

Ready-for use liquid 10%

< 25

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Respiratory Syncytial Virus Antibodies

Class Summary

Prevention of RSV infection in immunodeficient infants and children is effective using either polyclonal high-titer human IVIG or the humanized mouse monoclonal IgG, palivizumab. The former may provide some protection against other respiratory infections.

Respiratory syncytial virus immune globulin (RespiGam)

Immune globulin preparation containing high titers of RSV-neutralizing antibody. Polyclonal IVIG may decrease incidence of RSV and other respiratory infections.

Palivizumab (Synagis)

Children with asymptomatic acyanotic congenital cardiac disease may be treated with palivizumab.

Because it is a specific anti-RSV antibody, it does not protect against other respiratory infections.

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Immunosuppressive Agents

Class Summary

Patients with immune dysregulation and autoimmunity often benefit from immunosuppression. Commonly used drugs include corticosteroids in combination with cyclosporine or tacrolimus. Cyclophosphamide and azathioprine are administered less commonly. These modalities are usually used in collaboration with hematologists, gastroenterologists, and rheumatologists.

Cyclosporine (Neoral, Sandimmune)

May control autoimmune enteropathy; functions to down-regulate T-cell activation and is used most often to prevent graft rejection of renal, liver, and cardiac transplants; also used as prophylaxis against GVHD.

Tacrolimus (Prograf)

Suppresses humoral immunity (T lymphocyte) activity. Acts via a separate pathway to decrease T-cell activation, similar to cyclosporine; has been effective in autoimmune enteropathy when response to cyclosporine was insufficient or erratic; most extensive experience is as therapy in liver transplantation.

Prednisone (Deltasone)

Prototypic corticosteroid drug; doses of other corticosteroids should be converted to prednisone equivalents; patients with immune dysregulation/autoimmunity syndromes receive chronic therapy over years and, thus, must be monitored for long-term toxicities, especially hypertension, cataracts, and osteoporosis; prednisolone is preferred in patients with hepatic disease because prednisone is converted to prednisolone in the liver.

Cyclophosphamide (Cytoxan, Neosar)

Traditional alkylator chemotherapeutic agent effective in various rheumatologic diseases (eg, systemic lupus erythematosus); individual patients with autoimmune hemolytic anemia and autoimmune enteropathy also have responded to therapy; specific dosage depends on the autoimmune disorder type and should be chosen in consultation with a specialist in that disease.

Azathioprine (Imuran)

Lengthy experience is available in the use of this drug for long-term management of inflammatory bowel disease and renal disease caused by autoimmunity; efficacy in immune dysregulation/autoimmunity is not as well documented; may allow administration of lower-dose corticosteroids.

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Vaccines

Class Summary

Sinopulmonary infections in children with T-cell disorders are common. Immunization of children against S pneumoniae infection is an important consideration.

Pneumococcal 7-valent conjugate vaccine (Prevnar)

Sterile solution of saccharides of capsular antigens of S pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to the diphtheria CRM197 protein. These 7 serotypes have been responsible for >80% of invasive pneumococcal disease in children < 6 y in the United States. S pneumoniae also accounts for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) and 100% of pneumococci with high-level penicillin resistance. Customary age for first dose is 2 mo, but can be given as young as 6 wk. Preferred sites of IM injection are anterolateral aspect of the thigh in infants or deltoid muscle of upper arm in toddlers and young children. Do not inject vaccine in gluteal area or areas in which a major nerve trunk or blood vessel may be located.

Ideally, it should be administered at ages 2 mo, 4 mo, and 6 mo, with a booster dose at 12-15 mo for a total of 4 injections. The following is a guideline for vaccinating infants and toddlers who do not meet this schedule: The number of 0.5-mL doses administered in infants receiving the first dose at age 7-11 mo is 3 (4 wk apart; third dose after first birthday), in children aged 12-23 mo is 2 (2 mo apart), and in children aged >24 mo through 9 y is 1.

Minor illnesses, such as a mild upper respiratory tract infection, with or without low-grade fever, are not generally contraindications.

Pneumococcal vaccine polyvalent (Pneumovax-23, Pnu-Imune 23)

Polyvalent vaccine used for prophylaxis against infection from S pneumoniae. Used in populations at increased risk of pneumococcal pneumonia (ie, age >55 y, chronic infection, asplenia, immunocompromised state).

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Tumor Necrosis Factor Inhibitors

Class Summary

TNF is a cytokine in which 2 forms have been identified with similar biologic properties. TNF-α or cachectin is produced predominantly by macrophages, and TNF-β or lymphotoxin is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that contributes to symptoms. Infliximab (Remicade), was the first one approved by FDA belonging to this category. Since then, 3 more TNF inhibitors are approved by FDA: etanercept (Enbrel), adalimumab (Humira), and certolizumab (Cimzia). They may be used for controlling autoimmune complications but clinical data for their use are limited in the diseases described in this paper.

Infliximab (Remicade)

Neutralizes cytokine TNF-α and inhibits it from binding to TNF-α receptor. Consult gastroenterologist for use.

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