eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology
T-Cell Disorders: Treatment & Medication
Updated: Jul 10, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Sinopulmonary infections with common viral and bacterial agents are characteristic of partial T-cell disorders. Conventional therapy appropriate for the immunologically healthy host is administered, although patients with T-cell defects characteristically have more prolonged and severe clinical courses. Prophylaxis against infection by respiratory syncytial virus (RSV) using RSV-polyclonal immunoglobulin or the humanized monoclonal antibody, palivizumab, is specifically indicated in patients with T-cell disorders. Mucocutaneous candidiasis is more frequent but is conventionally treated in patients, and the disease uncommonly disseminates.
- Bone marrow transplantation must be offered early in infancy to patients with Wiskott-Aldrich syndrome (WAS) to ensure better outcome. In addition, transplantation is the only effective treatment in most patients with Chediak-Higashi syndrome (CHS) and is indicated prior to development of the accelerated phase. Patients with DiGeorge syndrome (DGS) rarely have complete absence of T-cell function; these few patients require stem cell reconstitution, usually via bone marrow transplantation.
- Routine childhood immunizations are usually indicated because patients with partial T-cell defects, even those with abnormalities in immunoglobulin levels, often respond with adequate specific antibody titers, although the levels may be lower than normal. However, administration of the oral live-attenuated poliovirus vaccine is contraindicated and should be replaced with the inactivated poliovirus vaccine. As a result of the frequency of bacterial sinopulmonary infections, administration of the conjugated pneumococcal vaccine (Prevnar) is particularly important.
- Usually, treatment in persons with autoimmune disorders mirrors that for hosts who are immunocompetent. However, infectious complications pose a greater risk in patients with T-cell disorders who receive systemic steroids and other immunosuppressive drugs.
- Overproduction of cytokines by T cells and other effector cells of the immune system can be controlled through use of anticytokine monoclonal antibodies, such as anti–tumor necrosis factor (TNF)–α (infliximab), for inflammatory bowel disease.
- Insulin-dependent diabetes mellitus (IDDM), hypoadrenalism, hypothyroidism, glomerulonephritis, and autoimmune enteropathy present in patients at unusually young ages, typically in patients younger than 1 year who have immune dysregulation/autoimmunity disorders.
- Patients with WAS and older patients who have chromosomal breakage syndromes (CBSs) have a high risk of malignancy. Chemotherapy in patients with ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) is not usually tolerated at conventional doses because of DNA instability. Thus, lower doses and longer intervals between doses are usually used.
- Gene therapy is being studied as a possible alternative to allogeneic hematopoietic stem cell transplantation for the treatment of severe combined immunodeficiency (SCID),5 as well as a treatment for WAS.6,7
- Several drugs that block the lymphocyte voltage-gated potassium channel, kv1.3, as well as biologic therapies, are being explored as autoimmune disease treatments.8,9
- Graft versus host disease (GVHD) has been prevented successfully in mice through ex vivo selection and expansion of CD4(+)CD25(+) immunoregulatory T cells, specific for recipient alloantigens.10
- Mesenchymal stem cells have shown some promise in enhancing engraftment and both preventing and treating GVHD in bone marrow transplant recipients.11
- Antithymocyte globulin has been shown to reduce acute and chronic GVHD in randomized trials.12
Surgical Care
- With the exception of cardiac procedures in patients with DGS, surgery is not usually required for patients with partial T-cell disorders.
- Splenectomy has been used to control autoimmune hemolytic anemia and thrombocytopenia in patients with WAS and immune dysregulation/autoimmunity syndromes. In patients with WAS and Fas and Fas ligand deficiencies, overwhelming postsplenectomy sepsis has occurred despite immunization and antibiotic prophylaxis directed against Streptococcus pneumoniae.
Consultations
- Clinical immunologists and geneticists are integral to the evaluation and treatment in patients with partial T-cell disorders.
- Intervention performed by neurologists is important in patients with CBSs and CHS.
- Physical therapists and rehabilitation specialists are critical to achieving optimal functioning in patients with CBSs and CHS.
- Autoimmune disorders are best controlled with the help of collaboration by hematologists, endocrinologists, and gastroenterologists.
- The malignancies in CBSs may require alteration of chemotherapeutic regimens because of the increased DNA instability of host cells.
- When a T-cell disorder is suspected, the Immune Deficiency Foundation offers a consultation service for physicians. Laboratories in Seattle (the University of Washington), Boston (Children's Hospital Boston), and New York City (The Jeffrey Modell Foundation) are funded to provide molecular analysis or can assist in contacting other research facilities.
Diet
- As with other primary immunodeficiencies, supplemental nutrition can be an essential component of care for the patient with chronic enteropathy or chronic infection.
- Unfortunately, many patients remain thin with short stature or become wasted.
Activity
- The goal of care is to optimize daily functioning. Care to minimize exposure to certain viruses (eg, RSV, varicella) is important, but complete isolation is not recommended for patients with partial T-cell disorders.
- Patients with WAS and CHS who have increased bleeding tendencies must be educated to avoid trauma and, especially, to wear helmets during certain activities.
Medication
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).
Immune Globulin, Intravenous13,14,15,16
Open table in new window
Table
| Brand(Manufacturer) | Manufacturing Process | pH | Additives* | 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) | 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 |
| Brand(Manufacturer) | Manufacturing Process | pH | Additives* | 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) | 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 |
*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).
Respiratory syncytial virus antibodies
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.
Adult
Severe RSV infection has not been recognized in adults with T-cell disorders
Pediatric
750 mg/kg IV qmo from November to April
May prevent active antibody response to live virus vaccine (eg, MMR); do not administer live virus vaccines until more than 9 mo after RSV-IVIG is discontinued
Documented hypersensitivity; cyanotic congenital cardiac disease
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
Adverse effects include fever and, possibly, headaches and nausea, as seen with IVIG; consider premedication with acetaminophen and diphenhydramine; patients with chronic pulmonary disease may require additional diuretics
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.
Adult
Severe RSV infection has not been recognized in adults with T-cell disorders
Pediatric
15 mg/kg IM qmo from November to April
None reported
Documented hypersensitivity; cyanotic congenital cardiac disease
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
Caution in thrombocytopenia or other coagulation disorders; compared to placebo, no increase in fever, rash, liver functions, or local reactions
Immunosuppressive agents
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.
Adult
5-10 mg/kg/d PO qd or in divided doses q12h; monitor trough levels in blood or serum after 3-5 d of stable dosing
Alternative: 5-6 mg/kg/d IV over 2-6 h when PO not tolerated or absorption is inadequate (eg, severe enteropathy)
Pediatric
Administer as in adults
CYP3A4 inducers (eg, carbamazepine, phenytoin, isoniazid, rifampin, phenobarbital) may decrease cyclosporine concentrations; CYP3A4 inhibitors (eg, azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, clarithromycin) may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UV-B radiation in psoriasis because risk of cancer may be increased
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 patients who cannot take PO; adverse effects include hirsutism, hypertension, acne, gingival hyperplasia, tremor, headache, leukopenia, hyperkalemia, hypomagnesemia, hyperuricemia, and renal and hepatic toxicity
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.
Adult
0.15-0.3 mg/kg/d PO divided q12h to maintain therapeutic trough blood levels; absorbed better without food
Alternative: 0.05-0.15 mg/kg/d IV infusion over 24 h
Pediatric
Administer as in adults
Levels may increase with diltiazem, nicardipine, clotrimazole, verapamil, erythromycin, ketoconazole, itraconazole, fluconazole, bromocriptine, grapefruit juice, metoclopramide, methylprednisolone, danazol, cyclosporine, cimetidine, clarithromycin; levels may decrease with rifabutin, rifampin, phenobarbital, phenytoin, and carbamazepine; metabolized via CYP3A4
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
Do not administer simultaneously with cyclosporine; tonic clonic seizures may occur; adverse effects are similar to those with cyclosporine; coagulation disorders have been reported; caution in renal or hepatic compromise (decrease dose)
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.
Adult
1-2 mg/kg/d PO divided q12h; not to exceed 80 mg/d; may be effective at qod intervals when autoimmune disease is in remission
Pediatric
Administer as in adults
Liquid preparation has unpalatable bitter taste; therefore, alternative is to crush tabs in small amounts of fruit syrup, applesauce, or foods preferred by children
Coadministration with estrogens may decrease prednisone 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; peptic ulcer disease; relatively contraindicated in hepatic dysfunction
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; may cause hypertension, hirsutism, tremor, gingival hyperplasia, and headache; monitoring is required for hypomagnesemia, hyperkalemia, hyperuricemia, hyperglycemia, nephrotoxicity, and hepatotoxicity; severity of disease associated with T-cell disorders requires careful surveillance, and appropriate exposure prophylaxes for certain infectious agents (most notably varicella, viral and fungal infections) are greater risks for infection but are not contraindications for continued steroid therapy
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.
Adult
PO: 50-500 mg qwk (dose depends on size and clinical response)
IV: 500-750 mg/m2 qmo after adequate hydration; not to exceed 1 g/dose
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile, particularly neutrophils and platelets, to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; institute adequate hydration before administration; long-term effects include infertility, malignancy, and, possibly, leukoencephalitis; dose-limiting toxicities include leukopenia and cardiomyopathy
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.
Adult
Initial: 3-5 mg/kg/d PO/IV
Maintenance: 1-3 mg/kg/d PO
Pediatric
Administer as in adults
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and monitor liver, renal, and hematologic functions; pancreatitis is rarely associated; adverse effects include myelosuppression, rash, GI tract symptoms, liver toxicity, hair loss, stomatitis, and arthralgias
Vaccines
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.
Adult
Not established
Pediatric
3 doses of 0.5 mL each at intervals >2 mo, followed by fourth dose of 0.5 mL at age 12-15 mo; recommended dosing interval is 4-8 wk; administer fourth dose 2 mo or more following third dose
Immunosuppressive agents (large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may reduce effectiveness; pneumococcal 7-valent conjugate vaccine may increase effects of anticoagulant therapy; therapy with immunoglobulin preparations is likely to block active immunity induced by pneumococcal vaccination (withhold Prevnar for 3 mo after discontinuation of immunoglobulin therapy)
Documented hypersensitivity; hypersensitivity to diphtheria toxoid; severe or moderate febrile illness; infants or children with thrombocytopenia or coagulation disorders that contraindicate IM injection unless potential benefit clearly outweighs risk of administration
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
For IM use only; do not administer IV under any circumstances; take special care to prevent injection into or near blood vessels or nerves; caution in patients with possible history of latex sensitivity (packaging contains dry natural rubber); use of pneumococcal conjugate vaccine does not replace use of 23-valent pneumococcal polysaccharide vaccination in children >24 mo with sickle cell disease, asplenia, HIV infection, chronic illness, or those who are immunocompromised; caution in coagulation disorders
Pneumococcal vaccine (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).
Adult
0.5 mL IM/SC single dose
Pediatric
<2 years: Contraindicated (antibody response is poor in this age group)
>2 years: Administer as in adults
Immunosuppressive agents (large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may reduce effectiveness; therapy with immunoglobulin preparations is likely to block active immunity induced by pneumococcal vaccination (withhold pneumococcal vaccine for 3 mo after discontinuation of immunoglobulin therapy)
Documented hypersensitivity; hypersensitivity to thimerosal; severe or moderate febrile illness; thrombocytopenia or coagulation disorders that contraindicate IM injection unless potential benefit clearly outweighs risk of administration
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
May cause arthralgia, fever, urticaria, and Guillain-Barré syndrome (rarely)
Tumor necrosis factor inhibitors
TNF is a cytokine in which 2 forms have been identified with similar biologic properties. TNF-a or cachectin is produced predominantly by macrophages, and TNF-b 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-a and inhibits it from binding to TNF-a receptor. Consult gastroenterologist for use.
Adult
5 mg/kg as single IV infusion
Pediatric
Not established (consult gastroenterologist)
None reported
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
TNF-a modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections
More on T-Cell Disorders |
| Overview: T-Cell Disorders |
| Differential Diagnoses & Workup: T-Cell Disorders |
 Treatment & Medication: T-Cell Disorders |
| Follow-up: T-Cell Disorders |
| Multimedia: T-Cell Disorders |
| References |
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References
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Further Reading
Keywords
T-cell disorders, cell-mediated immunodeficiency, DiGeorge syndrome, DGS, ataxia telangiectasia, AT, Wiskott-Aldrich syndrome, WAS, Chediak-Higashi syndrome, CHS, chromosomal breakage syndromes, CBSs, severe combined immunodeficiency, SCID, Omenn syndrome, cartilage-hair hypoplasia, DiGeorge syndrome, DGS, IPEX syndrome, XPID, candidiasis, diarrhea, lymphoproliferation, bone marrow transplantation, hypothyroidism, lymphoproliferative disease, atopic dermatitis, Nijmegen breakage syndrome, NBS, hematopoietic stem cell transplantation, treatment, diagnosis
