Introduction to Primary Immunodeficiencies PDF

Introduction to Primary Immunodeficiencies Lee Scott, M.D. Objectives Explain the differences between primary and secondary immunodeficiencies. Recognize clinical presentations of primary immunodeficiencies (PID), including non-infection presentations/manifestations. Name the PIDs most commonly asso...

Introduction to Primary Immunodeficiencies Lee Scott, M.D. Objectives Explain the differences between primary and secondary immunodeficiencies. Recognize clinical presentations of primary immunodeficiencies (PID), including non-infection presentations/manifestations. Name the PIDs most commonly associated with autoimmune or chronic inflammatory diseases. Recognize the known syndrome complexes that are associated with PIDs. Identify patients who should be evaluated for PIDs. Describe the broad categories of PIDs. Name the specific organisms/infection types associated with each PID category. List the initial labs that are most helpful for each PID category. Explain basic principles of treatment of PIDs. (Do not memorize Slide 27.) List the cancers most commonly associated with PIDs. Name the PIDs with the highest rates of cancer. Immuno – deficiency Essentially, something is wrong with the immune system What happens if something goes wrong with the immune system? Infection! Immunodeficiencies can be ….. Primary (previously called congenital) The immunodeficiency is the primary problem. Almost always genetic/inherited. Some acquired forms have been described. Secondary There is some underlying problem leading to the immunodeficiency: Infection (HIV) Malnutrition Medication (corticosteroids) Primary Immunodeficiencies (PID) PIDs are not rare. IgA deficiency is the most common 1 in 300 - 500 people in the U.S., (estimated) non- IgA deficiency PID 1 in 1200 live births. PIDs can present at any age. PIDs can range from mild to severe. There are MANY PIDs ( more than 450) You should always keep PID in mind regardless of the specialty that you choose. Identification and treatment of PID can be at a minimum, life-altering, and is often life-saving! Primary Immunodeficiency Diseases PID Manifestations PID may be recognized because of: §Increased susceptibility to infection (Hallmark) §Autoimmune dz §Chronic inflammatory dz §A syndrome complex §Children with PID tend to also have: Chronic diarrhea “Failure to thrive” (growth faltering) (poor weight gain) Autoimmune or Chronic Inflammatory Dz PID patients may present with autoimmune or chronic inflammatory diseases. Systemic lupus erythematosus Rheumatoid arthritis Autoimmune thrombocytopenia Autoimmune hemolytic anemia Vasculitis Autoimmune Thyroiditis Watch for signs of PID in these patients. The PIDs most commonly associated autoimmune or chronic inflammatory diseases are: !! Common Variable Immunodeficiency (CVID) Selective IgA deficiency Chronic mucocutaneous candidiasis Complement pathway deficiencies -MSK! Syndrome Complexes PID can also be seen as part of a constellation of signs and symptoms in a syndrome complex. DiGeorge Syndrome Congenital Heart Disease Hypoparathyroidism Cause hypocalcemia Abnormal facies Low set ears Microagnathia - underdeveloped jaw Hypertelorism - increased distance between eyes Thymic hypoplasia **** Embryology: pharyngeal pouch development You may be able to diagnose the PID before symptoms manifest! Syndrome Complexes cont’d Ataxia-Telangiectasia Ataxia Telangiectasia small dilated blood vessels near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter Wiskott-Aldrich Thrombocytopenia Eczema These are both associated with Variable B- and T- cell dysfunction. Infection Increased susceptibility to infection is the hallmark of PID. Patients will typically have chronic or recurrent infections. These are usually “routine” infections: Otitis Sinusitis Pulmonary infections For this reason, PID is often undetected initially. Sometimes, one or more of the infections is: unusually severe. Sepsis leads to an unexpected complication. Empyema, fistula caused by an organism of relatively low virulence. Aspergillus Note 1: If the infection is always in the same location, this is more likely a mechanical issue. Example: Recurrent right maxillary sinus infection, most likely a problem with the drainage of that one sinus. Note 2: Smokers get recurrent sinus and lung infections. This is usually due to the smoking rather than a PID. “Normal” infection rates Children tend to get multiple viral infections during the first years of life. Especially if they attend daycare. These infections are usually self-limiting. Children under 2 are more likely to get ear infections due to eustachian tube position. Healthy older children and adults rarely get ear infections. Babies get thrush. Healthy older children and adults rarely get thrush. Healthy children, teens, and adults generally only get sick a few times a year and do not often require antibiotics. Evaluate any patient with 2 or more of these for PRIMARY Immunodeficiency Make sure that you’ve considered the possibility of a SECONDARY Immunodeficiency. Lifelong infection history + FH more in line with PID. New onset infections without FH more likely 2°. PID Categories Innate Immunodeficiencies Adaptive Immunodeficiencies Phagocytic deficiencies Complement deficiencies B-cell/Ab deficiencies T-cell deficiencies Combined B & T cell deficiencies B-cell/Antibody Immunodeficiencies The most common type of PID ›50% of all PID diagnoses May be characterized by presence or absence of B-cells Usually present after 3-6 months of life (maternal Abs are gone!) Increased susceptibility to respiratory tract infections with bacteria Streptococcus pneumoniae Haemophilus influenza Often present with sinopulmonary infections (often severe) Otitis media Sinusitis Pneumonia and Diarrhea X-linked agammaglobulinemia Selective IgA deficiency (most common B cell ds) Common Variable Immunodeficiency (CVID) -at least two Ig levels are low T-cell and Combined (CID) Defects Presentation and severity depend on the specific defect. Usually present early in life. May be characterized by presence or absence of T-cells. T-cells are important to normal functioning of B-cells, so Combined T-cell and B-cell disorders are common T-cell and Combined (CID) Defects Severe Combined Immunodeficiency (SCID) The most severe forms of CID (T-, B+) (T-, B-) “Bubble Boy” Virtually no T cells or immune function Present within first year of life Chronic diarrhea Failure to thrive Skin rashes Opportunistic infections Thrush Pneumocystis T cell Defects -Viruses -Fungi -Pneumocystis Pediatric Emergency Treat with bone marrow transplant ASAP !! Most states now screen for this at birth Rare, but deadly David Phillip Vetter 1971-1984 T-cell and Combined (CID) Defects Less severe disorders may present later in childhood. Wiskott-Aldrich Syndrome DiGeorge Syndrome Ataxia-Telangiectasia X-linked lymphoproliferative ds Innate Immunodeficiencies May present at any age Complement Disorders Encapsulated Organisms C3: S. pneumonia H. influenza C5-9 Neisseria meningitidis Meningitis Sepsis Arthritis Innate Immunodeficiencies Phagocytic Disorders Abnormalities of neutrophils or monocytes Chronic granulomatous disease is most common Pyogenic (pus-like) bacterial and fungal infections common Skin Respiratory tract Internal organs Painful sores around mouth common Initial evaluation options Suspected B-cell/Ab disease: Immunoglobulin levels Response to vaccinations IgG titers Suspected Complement deficiency CH50 Assay o C1-C9 o If abnormal, order additional testing. Initial evaluation options Suspected T-cell disorders: HIV clinically resembles T-cell ds CBC Lymphocytopenia Lymphocyte subset analysis T-cells (CD3, CD4, CD8) B-cells (CD19, CD20) Natural Killer cells (CD16, CD56) *See Next Slide Suspected Phagocytic disorders: CBC Neutropenia PID treatment and management Increased Cancer Risk in PID Overall Cancer Risk for PID patients: 4 to 25 percent Advances in the treatment of PID longer life expectancies corresponding increase in malignancies. The most common types of cancer in patients with PID non-Hodgkin lymphoma (NHL) Hodgkin lymphoma 60% of malignancy cases Cancers in PID are more likely to be widespread at the time of diagnosis. present at somewhat younger ages. died of Burkitt’s lymphoma Increased Cancer Risk in PID Non-Hodgkin lymphoma (NHL) in patients with PID tend to be of: B-cell origin high histologic grades associated with Epstein-Barr virus infection extra-nodal tissues gastrointestinal tract central nervous system. PIDs with the highest incidences of cancers (Hodgkin and Non-Hodgkin lymphoma) are: ataxia-telangiectasia (30%) common variable immunodeficiency (24%) Wiskott-Aldrich +SCID+ Selective IgA deficiency (~1/3) Increased Cancer Risk in PID Educate patients on symptoms to report: Weight loss Recurrent fever Soaking night sweats Easy bruising or bleeding Prolonged tiredness Educate patients on general recommendations for cancer prevention: Avoid STIs Don’t smoke Don’t drink excessively Maintain healthy weight [email protected] Rm. 215