Key Points
- Primary immunodeficiency diseases (PIDDs) are inherited disorders of immune system function that predispose affected subjects to an increased rate and severity of infection, immune dysregulation with autoimmune disease and aberrant inflammatory responses, and malignancy.
- Primary immunodeficiencies are distinct from secondary immunodeficiencies that occur, for example, during certain viral infections, after immunosuppression to prevent graft rejection after transplantation, during treatment of systemic autoimmune disease, and in association with cancer chemotherapy.
- Primary immunodeficiencies occur in as many as 1:2000 live births.
- The principal clinical manifestation of immunodeficiency is increased susceptibility to infection.
- Autoimmune disease and malignancy are also often seen in a variety of immunodeficiencies.
- In the course of evaluating immunodeficiency, it is critical, as much as possible, to document carefully the foci of infections, the organisms, and the response to treatment.
- This is necessary to distinguish infectious disease from other noninfectious conditions, such as allergy, or to distinguish viral infection from bacterial infection.
- Any other conditions that might predispose to infection, including anatomic defects, allergy, and metabolic disorders, should be considered where appropriate.
- However, also note that hypersensitivity to environmental allergens, food allergens, or both might be an important element of and diagnostic clue for a variety of PIDDs.
Diagnosis
General Considerations
- SS 1. It is critical to maintain a high index of suspicion for PIDDs in patients presenting with recurrent infections, autoimmune disease, malignancy, and combinations of these conditions (D).
- SS 2. Other conditions that can increase susceptibility to infection should be sought in patients with suspected PIDDs. (D)
- SS 3. It is important to confirm the precise focus of infection and organism when possible in any patient with known or suspected PIDDs. (F)
- SS 4. A focused family history (eg, recurrent infections, absence of infections in siblings, early childhood deaths, and diagnosed PIDDs) should be obtained when the differential diagnosis includes a PIDD. (D)
- SS 5. A stepwise approach is recommended to evaluate suspected PIDDs. (D)
- SS 6. Evaluation of specific immune responses is essential for diagnosis of PIDDs. (C)
- SS 7. PIDDs should be defined at the molecular genetic level if management can be affected. (F)
- SS 8. The possibility of an X-linked PIDD should be considered, even in female patients, when other possibilities have been ruled out. (D)
- SS 9. Carrier status should be determined for all potentially affected relatives of patients with severe PIDDs. (D)
Table 1. Characteristic Clinical Presentations of Some Immunodeficiency Disorders
Diagnosis | Symptoms and/or clinical presentation |
---|---|
Combined Immunodeficiencies | |
SCID | Failure to thrive, diarrhea, severe/disseminated infections, opportunistic infections, rash; abnormal newborn screena |
CD40L deficiency | Recurrent serious pyogenic infections, opportunistic infections (PCP) |
Immunodeficiency syndromes | |
WAS | Thrombocytopenia with bleeding and bruising, eczema, recurrent infection with encapsulated organisms, autoimmunity |
AT | Chronic sinopulmonary disease, cerebellar ataxia, oculocutaneous telangiectasia, malignancy |
DGS | Hypocalcemic seizures caused by hypoparathyroidism, cardiac disease, abnormal facies, infection, abnormal newborn screena |
Antibody deficiency | Recurrent sinopulmonary infections with encapsulated bacteria, recurrent viral respiratory tract and gastrointestinal infections |
Immune dysregulation | Autoimmunity, lymphoproliferation, HLH |
Phagocytic cell defects | |
CGD | Deep-seated infection, abscess with granuloma formation |
LAD | Recurrent serious bacterial infections, delayed separation of the umbilical cord; poor wound healing, lack of pus |
HIES type 1 | Chronic dermatitis, recurrent serious infection of the lungs with pneumatoceles; skin infections, bone fragility, failure to shed primary teeth |
MSMD | Severe mycobacterial and Salmonella species infections |
Innate immune defects | |
NEMO deficiency | Severe bacterial infections, opportunistic infections, anhidrotic ectodermal dysplasia |
IRAK-4 defect | Severe gram-positive bacterial infections in early childhood |
CMCC | Chronic skin and mucous membrane fungal infections |
HSE | Herpes simplex encephalitis |
EV | Severe disseminated cutaneous papillomatosis |
Autoinflammatory disorders | Episodic fever often associated with dermatitis, gastrointestinal symptoms, and arthropathy |
Complement deficiency | Recurrent bacterial infections (encapsulated strains, Neisseria species), autoimmunity |
Immunodeficiency associated with autoantibodies | |
Anti–GM-CSF autoantibodies | Cryptococcal meningitis and PAP (alone or together) |
Anti–IFN-γ autoantibodies | Disseminated infections with mycobacteria, Salmonella species, Cryptococcus species, Histoplasma species, Penicillium species, and varicella-zoster virus |
Table 2. Laboratory Tests of Immune Function
Screening tests | Advanced tests |
---|---|
Humoral immunity | |
Serum immunoglobulin levels | Flow cytometry to enumerate B-cell subsets (eg, naïve and switched memory cells) |
Serum specific antibody titers | In vitro immunoglobulin production in response to mitogens or other stimuli |
Antibody response to booster immunization | Antibody response to immunization with ΦΧ174 |
Flow cytometry to enumerate total B cells | |
Cellular immunity | |
TREC newborn screening | Flow cytometry to enumerate T-cell subsets (eg, naïve, memory, and activated cells) |
Flow cytometry to enumerate CD4 and CD8 T cells and NK cells | In vitro proliferative response to mitogens and antigens |
Cutaneous delayed hypersensitivity | T-cell cytotoxicity |
Spontaneous NK cytotoxicity | In vitro surface marker expression and cytokine production in response to stimuli |
Cytoplasmic protein phosphorylation in response to stimuli | |
Phagocytic cells | |
Blood cell count with differential | Chemotaxis and/or phagocytosis assay |
Neutrophil staining, morphology on a peripheral blood smear | Enzyme assays (myeloperoxidase, G6PDH) |
DHR reduction or nitroblue tetrazolium | WBC turnover |
Flow cytometry for adhesion molecules | Bacterial or fungal killing |
Bone marrow biopsy | |
Complement | |
CH50 assay (total hemolytic complement activity) | Level or function of individual complement components |
AH50 assay (alternative pathway hemolytic activity) | |
Lectin pathway function | |
Genetic tests | |
Microarray for copy number variation | Targeted gene sequencing |
Whole-exome/genome sequencing |
Table 3. Summary of Laboratory Findings in the Diagnosis of Antibody Deficiencies
IgG | IgA | IgM | IgG subclass | Vaccine response | B cells | Diagnosis |
---|---|---|---|---|---|---|
NL | NL | NL | NL | NL | NL | Normala |
NL | NL | NL | NL | Lowb | NL | SAD |
NL | NL | NL | ≥1 Low | Lowb | NL | IGGSD |
NL | Absent | NL | Normal | NL or low | NL | SIGAD |
NL | Absent | NL | ≥1 Low | Lowb | NL | IgA deficiency with IGGSD |
Low | NL | NL | NL | NL | Possible secondary, unspecified, or transient hypogammaglobulinemiac | |
Low | NL or low | NL or low | NL | NL or low | Unspecified or transient hypogammaglobulinemia | |
Low | Low | NL or high | Low | NL | HIM | |
Low | Low | NL or low | Lowd | NL or low | CVID, possible transient hypogammaglobulinemia | |
Absent | Absent | Absent | Absent | Agammaglobulinemia or severe CVIDe |
a Consider complement deficiency or phagocyte defect.
b Usually refers to polysaccharide response.
c In this circumstance it is useful to measure serum total protein and/or albumin levels. If low, this is consistent with secondary hypogammaglobulinemia.
d Protein and/or polysaccharide response.
e Cellular immunity should be evaluated as indicated by other clinical features but is often worth considering when significant impairment of humoral immunity is observed because it could be a component of a CID.
Treatment
- SS 10. After diagnosis of a PIDD, it is important to proceed quickly with preventive therapy, replacement therapy, or both. (C)
- SS 11. Immunoglobulin replacement therapy is indicated for all disorders with significantly impaired antibody production. (B)
- SS 12. In association with low IgG levels, IgA deficiency is not a contraindication to IgG therapy. (C)
- SS 13. Patients receiving IgG therapy should have regular monitoring of IgG trough levels, blood cell counts, and serum chemistry. (D)
- SS 14. The placement of permanent central venous access solely for the purpose of IVIG administration should be discouraged. (F)
- SS 15. Aggressive and prolonged antimicrobial therapy should be considered for immunodeficient patients. (C)
- SS 16. Short- or long-term antimicrobial prophylaxis should be considered for patients with immunodeficiency. (C)
- SS 17. Lung imaging and function should be monitored regularly in patients with a history of or who are at risk for recurrent pneumonia and/or other chronic lung damage or disease. (C)
- SS 18. Surgical procedures undertaken with the aim of reducing infection susceptibility should be approached with caution in patients with known or suspected PIDDs. (F)
- SS 19. The recommended definitive therapy of cellular or combined PIDD is reconstitution by hematopoietic stem cells. (B)
- SS 20. Only irradiated, CMV-negative, lymphocyte-depleted cellular blood products should be administered to patients with cellular or combined PIDDs. (C)
- SS 21. Live vaccines should not be administered to patients with severely impaired specific immunity. (C)
- SS 22. Inactivated or subunit vaccines can be administered to immunocompromised patients. (C)
- SS 23. Education for patients and families with PIDDs is recommended for optimal outcomes. (F)
- SS 24. Patients with suspected or diagnosed PIDDs are recommended to have evaluation and follow-up by a clinical immunologist with experience with these disorders. (F)
- SS 25. A coordinated multidisciplinary approach to management should be considered in patients with PIDDs. (F)
Table 4. Summary of Therapeutic Considerations for Primary Immunodeficiencies and Their Complications
Diagnosis | IgGa | HSCT | Gene therapy | |
---|---|---|---|---|
CIDs | ||||
SCID (IL2RG, ADA) | Yes | Yes | Yes |
|
SCID (other) | Yes | Yes | No | |
CD40L deficiency | Yes | Yes | No | |
Other CID | Yes | Many | No | |
Immunodeficiency syndromes | ||||
WAS | Yes | Yes | Yes |
|
AT | Some | No | No | |
DGS | Some | No | No | |
Other syndromes | Some | Some | No | |
Antibody deficiency | ||||
Agammaglobulinemia | Yes | No | No |
|
CVID | Yes | Rare | No | |
Other antibody deficiency | Yes | No | No | |
Immune dysregulation | ||||
FHL | No | Yes | No |
|
ALPS | No | Yes | No | |
IPEX | No | Yes | No | |
APECED | No | No | No | |
Other | Some | Some | No | |
Phagocytic cell defects | ||||
Neutropenia | No | Yes | No |
|
CGD | No | Yes | Yes | |
LAD | No | Yes | No | |
HIES type 1 | Some | Rare | No | |
MSMD | No | Some | No | |
Innate immune defects | ||||
NEMO deficiency, other NF-κB defects | Yes | Yes | No |
|
CMCC | No | No | No | |
WHIM syndrome | Yes | Some | No | |
HSE | No | No | No | |
EV | No | No | No | |
Autoinflammatory disorders | No | No | No |
|
Complement deficiency | No | No | No |
|
Cytokine autoantibody-mediated disorders | Possible | No | No |
|
Table 5. Regimens for Prophylaxis of Bacterial Respiratory Tract Infections
Antibiotic | Regimen for children | Regimen for adults |
---|---|---|
Oral agentsa | ||
Amoxicillin (consider with clavulanate, if necessary) | 10-20 mg/kg daily or twice daily | 500-1,000 mg daily or twice daily |
Trimethoprim (TMP)/ sulfamethoxazole dosing for TMP) | 5 mg/kg daily or twice daily | 160 mg daily or twice daily |
10 mg/kg weekly or 5 mg/kg every other day | 500 mg weekly or 250 mg every other day | |
7.5 mg/kg daily or twice daily | 500 mg daily or twice daily | |
Age >8 y: 25-50 mg daily or twice daily | 100 mg daily or twice daily | |
Inhaled agents | ||
Age >6 y: 80 mg twice daily, 28 days on, 28 days off, OR 21 days on, 7 days off | ||
Age >6 y: 300 mg twice daily, 28 days on, 28 days off |
Combined B- and T-Cell Immunodeficiencies
Combined B- and T-Cell Immunodeficiencies
Severe combined immunodeficiency (SCID)
- SS 26. SCID should be considered in the differential diagnosis when an infant presents with recurrent, persistent, or severe bacterial, viral, or fungal infections or failure to thrive. (C)
- SS 27. Patients with SCID or suspected SCID should receive IgG replacement therapy. (C)
- SS 28. Patients with SCID or suspected SCID should be protected from exposure to infectious agents. (C)
- SS 29. Patients with SCID should receive PCP prophylaxis. (C)
- SS 30. Early signs of infection should be promptly investigated and antimicrobial regimens initiated and for prolonged periods. (C)
- SS 31. Polyethylene glycol (PEG)-conjugated ADA (PEG-ADA) should be administered to patients with SCID caused by ADA deficiency if HSCT or gene therapy is unavailable. (C)
- SS 32. A suspicion of SCID should be considered an urgent clinical condition. (C)
- SS 33. Patients with SCID should be immunologically reconstituted by means of HSCT or gene therapy. (B)
Table 6. Clinical and Laboratory Manifestations of Selected Combined Immunodeficiencies and Syndromes
Gene defect(s) or disease(s) | Clinical features | Laboratory features |
---|---|---|
Ca/Mg channel defects (MAGT1, ORAI1, STIM1) | Severe and opportunistic infections, autoimmune disease, anhydrotic ectodermal dysplasia, myopathy | Normal T-cell numbers, ↓ T-cell function |
CARD11 | Opportunistic infections | Hypogammaglobulinemia, normal lymphocyte numbers, ↓ T-cell function |
CD27 | Persistent symptomatic EBV viremia, recurrent infection | Hypogammaglobulinemia, impaired specific antibody response, decreased mitogen proliferation |
CD3G | Variable severity, SCID or mild phenotype, autoimmune hemolytic anemia | Modest ↓ CD8 T cells, ↓ CD45RA+ cells, ↓ TCR expression, variable immunoglobulins |
CD8 | Recurrent bacterial respiratory tract infections, bronchiectasis | Absent CD8 T cells, ↑ double-negative T cells |
CTLA4 | Autosomal dominant, lymphoproliferation, organ infiltration, lymphoma, respiratory tract infections | ↓ CD4 T cells, ↓ B cells, hypogammaglobulinemia, ↑ T-cell proliferation |
CTPS1 | Disseminated infections with EBV and varicella-zoster virus, encapsulated bacteria, B-cell lymphoma | Lymphopenia, ↓ naïve CD4 cells, ↓ IgG2, ↓ pneumococcal response, ↓ memory B cells, absent invariant NK T cells, ↓ PHA proliferation |
FOXN1 | Athymia, reduced T-cell numbers, absence of hair, and nail dysplasia | ↓ Naïve T cells; ↑ double negative (CD4– CD8)– T cells |
IKZF1 | Prematurity, polyhydramnios with fetal hydrops, neonatal pancytopenia | Normal lymphocyte numbers, absent B cells, ↓ NK cells, ↓ CD45RO+ T cells, absent mitogen proliferations, ↓ IgG |
IL21R | Respiratory tract infections, failure to thrive, diarrhea, cryptosporidiosis | Normal lymphocyte numbers, ↑ IgE, ↓ specific antibody, normal T-cell function, ↓ NK cytotoxicity |
ITK | EBV-associated lymphoproliferation, lymphoma | Lymphopenia, hypogammaglobulinemia |
MHC class I deficiency (TAP1, TAP2, TAPBP), CD8A | Variable severity, recurrent respiratory tract infections, bronchiectasis | Complete absence of CD8+ cells, normal CD4 cells, normal T-cell proliferation, normal immunoglobulins and antibody |
MHC class II deficiency (MHC2TA, RFX5, RFXANK, RFXAP), and LCK mutation | Severe and opportunistic infections, diarrhea, malabsorption, failure to thrive | ↓ CD4 T cells, normal CD8 cells; ↓ T-cell proliferation, hypogammaglobulinemia, ↓ antibody |
NP | Severe and opportunistic infections, severe varicella (including vaccine strain), neurological impairment | ↓ T cells, variable ↓ in B cells, ↓ T-cell proliferation, variable immunoglobulins and antibody |
PGM3 | Recurrent infections, skeletal dysplasia, developmental delay | Neutropenia, lymphopenia (↓ T and B cells), bone marrow failure |
POLE1 | Mild facial dysmorphism, livedo, short stature, recurrent pulmonary infection with bronchiectasis, recurrent Streptococcus pneumoniae meningitis, long-bone abnormalities | ↓ IgM, ↓ IgG2, ↓ isohemagglutinin, ↓ CD27+ memory B cells, low naïve T-cell numbers |
SLC46A1 | Severe opportunistic infections, failure to thrive (reversible with folate administration) | Normocytic anemia, ↓ serum folate, hypogammaglobulinemia, ↓ T-cell proliferation |
RHOH deficiency | Warts, molluscum, granulomatosis, Burkitt lymphoma | ↓ CD4 T cells, normal immunoglobulins and antibody |
STAT5B | Growth failure, ichthyosis/eczema, diarrhea ± bacterial or opportunistic infections, autoimmune disease | ↓ Insulin-like growth factor, ↑ growth hormone, ↓ T cells, especially ↓ Treg cells |
Trisomy 21 | Cognitive impairment, characteristic facies, cardiac defects, gastrointestinal disorders, hypothyroidism, recurrent respiratory tract infections | Variable T- and B-cell lymphopenia, ↓ naïve T and B cells, IGGSD, poor vaccine response, ↓ in vitro T-cell proliferation, ↓ neutrophil chemotaxis |
TRNT1 | Sideroblastic anemia, periodic fevers, developmental delay, sensorineural hearing loss, cardiomyopathy, CNS abnormalities | Variable ↓ immunoglobulins, ↓ B cells, progressive ↓ T cells and NK cells |
ZAP70 | Variable severity, SCID, and opportunistic infections, failure to thrive, mild phenotypes | ↓ CD8 T cells, normal CD4 cells, ↓ T-cell proliferation, hypogammaglobulinemia, ↓ antibody |
Table 7. Lymphocyte Phenotype Classification of SCID
Disease | Genes |
---|---|
T–B–NK– | |
Adenosine deaminase | ADA |
Adenylate kinase (reticular dysgenesis) | AK2 |
T–B–NK+ | |
Artemis | DCLRE1C |
Cernunnos | NHEJ1 |
DNA-dependent protein kinase | PRKDC |
DNA ligase IV | LIG4 |
RAG1 and RAG2 | RAG1, RAG2 |
T–B+NK– | |
X-linked SCID | IL2RG |
JAK3 deficiency | JAK3 |
CD25 deficiency | IL2RA |
T–B+NK+ | |
CD3 complex defects | CD3D, CD3E, CD3Z |
Coronin 1A deficiency | CORO1A |
CD45 deficiency | PTPRC |
IL-7 receptor deficiency | IL7RA |
Other CID syndromes
- SS 34. Patients with CID with intermediate T-cell numbers and function should be studied for leaky SCID or one of several CID syndromes based on clinical and laboratory characteristics. (C)
- SS 35. All forms of ancillary or supportive therapy administered to patients with SCID should be considered for patients with leaky SCID or non-SCID combined immunodeficiency. (C)
- SS 36. Patients with leaky SCID or a non-SCID combined immunodeficiency should be considered for stem cell therapy or gene therapy on a case-by-case basis. (C)
Hyper-IgM syndrome (HIM) caused by defects of CD40L and CD40
- SS 37. The diagnosis of a form of HIM should be considered in patients with very low IgG, IgA, and IgE levels and normal or increased IgM levels. (C)
- SS 38. CD40L expression should be evaluated by using flow cytometric methods on activated T cells. (C)
- SS 39. CD40 expression should be measured by using flow cytometry on monocytes or B cells. (C)
- SS 40. Female patients with the HIM phenotype should be studied for CD40L mutation if the CD40 mutation or another known mutation associated with the HIM phenotype is not found. (C)
- SS 41. PCP prophylaxis is indicated for all patients with known or suspected CD40 or CD40L deficiency. (C)
- SS 42. Neutropenia in patients with CD40 or CD40L deficiency should be treated with granulocyte colony-stimulating factor (G-CSF). (C)
- SS 43. HSCT should be considered for CD40L and CD40 deficiency. (C)
CID, unspecified
- SS 45. Any patient with abnormal serum immunoglobulin levels, specific antibody production, or both and evidence of impaired cellular immunity who does not fulfill the clinical and laboratory diagnostic criteria for any of the above disorders should be given a diagnosis of unspecified CID. (D)
Well-Defined Syndromes with Immunodeficiency
Well-Defined Syndromes with Immunodeficiency
- SS 46. A diagnosis of Wiskott-Aldrich Syndrome (WAS) should be considered in all male patients with clinically significant thrombocytopenia and small platelets. (C)
- SS 47. Patients suspected to have WAS should have a definitive molecular diagnosis by finding a known deleterious WAS mutation and/or abnormal WAS protein expression, which might be helpful for prognosis. (C)
- SS 48. Management of patients with WAS should include IgG replacement. (C)
- SS 49. HSCT must be seriously considered for patients <5 years of age with suitable stem cell donors. (C)
Non-SCID DNA repair defects
- SS 50. AT and other chromosomal repair disorders should be considered in all children with frequent infections and characteristic neurological, skeletal, and/or cutaneous manifestations, including ataxia, microcephaly, and telangiectasia. (C)
- SS 51. Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome should be considered in patients with abnormal facies, developmental delay, and immunodeficiency. (C)
- SS 52. Postmeiotic segregation increased 2 (PMS2) defects should be sought in patients with dysgammaglobulinemia, cafe-au-lait spots, and colon and/or brain tumors. (C)
- SS 53. A diagnosis of radiosensitivity, immunodeficiency, dysmorphic features, and difficult learning (RIDDLE) syndrome should be suspected in patients with developmental delay, short stature, dysmorphic facies, and hypogammaglobulinemia. (C)
- SS 54. Cytogenetic abnormalities, such as chromosomal translocations and chromosome fragility, support a diagnosis of AT or other chromosomal repair disorders. (C)
- SS 55. Patients suspected to have AT should be screened by measuring the serum α-fetoprotein (AFP) level (C).
- SS 56. Imaging with radiography should be used cautiously in patients with AT or other chromosomal repair disorders. (C)
- SS 57. Antibiotic prophylaxis, IgG replacement therapy, or both are indicated for patients with AT or other chromosomal repair disorders with increased susceptibility to infections. (C)
- SS 58. Management of malignancy in patients with AT and related disorders must be individualized. (C)
- SS 59. Stem cell transplantation can be considered in selected patients with AT and related disorders. (C)
DiGeorge syndrome (DGS)
- SS 60. DGS should be investigated in patients with thymic hypoplasia, cardiovascular structural defects, midline craniofacial defects, and hypoparathyroidism. (C)
- SS 61. Periodic immunologic re-evaluation is recommended for patients with DGS. (C)
- SS 62. Patients suspected of having DGS should have molecular testing for deletion of chromosome 22q11.2 or 10p14-13 by using fluorescence in situ hybridization or a genomic DNA microarray. (C)
- SS 63. Treatment of infants with complete DGS requires some form of T-cell reconstitution. (C)
Idiopathic CD4 lymphopenia (ICD4L)
- SS 64. ICD4L should be suspected in patients with opportunistic infections and persistent CD4 T-cell counts of <300 cells/μL in the absence of HIV infection or another cause of lymphopenia. (D)
- SS 65. Management of ICD4L is supportive and dictated by the degree of immune compromise. (D)
Immuno-osseous dysplasias
- SS 66. The immuno-osseous dysplasias should be considered in patients with severe growth retardation, skeletal abnormalities, and T-cell lymphopenia. (C)
- SS 67. Medical management of immunoosseous syndromes should include antibiotic prophylaxis and IgG supplementation appropriate to the severity of the immune dysfunction. (C)
- SS 68. HSCT is indicated and has been successful for the correction of hematologic and immunologic defects in patients with CHH. (C)
Comel-Netherton syndrome
- SS 69. A diagnosis of Comel-Netherton syndrome (SPINK5 gene mutation) should be sought in patients with abnormal hair structure, ichthyosis, allergic disease, and increased IgE and low IgG levels. (C)
Hyper-IgE syndromes (HIES)
- SS 70. A form of HIES should be considered in patients with recurrent sinopulmonary and skin infections, chronic eczematous dermatitis, high serum IgE levels, and eosinophilia. (C)
- SS 71. The initial approach to HIES therapy should be directed toward management of complications. (C)
- SS 72. Patients with DOCK8 deficiency and poor antibody production should receive IgG replacement therapy. (C)
- SS 73. The use of IVIG or IFN-γ in patients with type 1 autosomal dominant HIES might be helpful in selected cases. (C)
- SS 74. HSCT should be considered for both forms of HIES. (C)
Hepatic veno-occlusive disease
- SS 75. Mutations in the SP110 gene should be sought in patients with hepatic veno-occlusive disease with immunodeficiency. (C)
Dyskeratosis congenita (DKC)
- SS 76. DKC should be investigated in patients with abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa. (C)
Defects of vitamin B12 and folate metabolism
- SS 77. Inborn errors of folate and vitamin B12 malabsorption should be considered in the differential diagnosis of SCID. (C)
- SS 78. Infants with severe vitamin B12 or folate deficiency should be treated aggressively with folate or cobalamin replacement as soon as the diagnosis is made. (C)