OSCE PID Flashcards
39-year-old female with a four year history of recurrent infections. She recently had a pneumonia requiring IV antibiotics and has had multiple episodes of sinusitis requiring antibiotics. She is a current smoker, has 2-3 alcoholic beverages a day, and works in retail. She has a cat and a dog. She has a history of Sjogrens. Her family history reveals that her father died of a “blood infection” at age 50.
a. Outline your approach including hx, px, invx
b. She is diagnosed with CVID. What is your management?
c. Counsel her on prognosis.
History:
- Gather hx surrounding infections in the past few years - what kind of infection? what symptoms did she have at the time? how were they treated? did she require abx (PO vs IV) and did she respond?
- Other types of infections? e.g. AOM, OM, absesses
- any investigations done at the time she was sick e.g. bloodwork, imaging, samples etc
- Ask about CPODS and AR - hx of seeing ENT previously? any procedures?
- ROS –> constitutional symptoms, autoimmune features, GI sx (e.g. diarrhea), recurring rashes (especially eczema)
- Any medications she is currently on or was on at the time? Specifically immunosuppresants
- Were the pathogens identified by chance?
- PMhx: Hx of atopy (particularly asthma, etc)? Hx of autoimmune disease or malignancies? Hx of CF or polyps?
- Current medications, allergies, family hx (esp consanguineous)
Physical exam:
- Vitals, weight, height
- H&N (polyps, signs of AR)
- CV/resp exam (crackles, wheeze, reduced air entry)
- GI –> HSM, lymphadenopathy, masses, etc
- Derm –> eczema, other types of rashes
DDx:
- PID –> CVID, HIES, CGD (less likely), ?IgA deficiency
- Secondary –> medications (e.g. ritux, steroids), malignancy, HIV
- Bronchiectasis (e.g. CF, PCD, COPD)
- CRS +/- NP, asthma
- Vasculitis –> EGPA, GPA, MPA
- ?ABPA, OA, HP
Investigations:
- Bloodwork: basic BW (CBCD, albumin, Cr/Ur, liver enzymes), ESR/CRP, SPEP, ANA, ANCAs, humoral deficiency work up (LSUB, IgA/M/E/G, vaccine titres)
- Imaging: CXR +/- CT chest
- PFTs
Management:
- Non-Pharm –> educate patient on the disease, ensure vaccines are up to date (avoid lives vaccines), annual influenza vaccine, at least annual review/health screen minimum (including physical exam, PFTs, AUS, +/- CT chest), baseline CT chest
- Pharm –> IG replacement (IV or SC) usually 0.4-0.6 g/kg q4wks if IV (aiming for IgG trough b/w 7-9), consider abx prophylaxis if significant recurrent infections, prompt treatment of infections, treat comorbidities (e.g. asthma)
Prognosis:
- Generally can lead a healthy life
- Death is related to complications due to chronic lung disease and malignancies - long term data showed about 20% of patients died by age 40-50s
You are seeing a patient with CVID who would like to start treatment.
a. How is the diagnosis of CVID made?
b. Please discuss the treatment options with her.
c. What are the complications of CVID? How would you monitor her?
Diagnosis:
- Low IgG and either low IgA or IgM
- Poor vaccine response
- Absence of other defined immunodeficiency state
Probably need hx of recurrent infections as well
Treatment options:
- Replace immunoglobulin either IV or SC
- Abx prophylaxis if recurrent infections
- Treat acute infections
- Ensure vaccines are up to date, avoid live vaccines
- Treat co-morbidities
- Regularly screen for complications –> at least annual spirometry/PFTs, AUS, physical exam +/- chest imaging (CXR or CT depending on their status), regular bloodwork (q6-12 mths)
Complications:
- Bronchiectasis, ILD
- Granulomas –> liver, GIT, lymph nodes etc
- Malignancy (e.g. lymphoma)
- Autoimmunity (e.g. AIHA, ITP, RA, autoimmune hepatitis, etc)
- GI disease (e.g. enteropathy, gastric CA, liver dysfunction)
- Lymphadenopathy, splenomegaly
Please see the picture below. –> child with light/blond hair and light eyes
a. What immunodeficiency is this consistent with?
b. What are the usual clinical findings?
c. What is the mutation and pathophysiology of this disease?
d. How would you manage this?
- Chediak Higashi Syndrome
- Recurrent pyogenic infections (skin, resp, mucous membranes), oculocutaneous albinism, coagulation defects (easy bruising, bleeding), oral disease (gingivitis, oral ulcerations, periodontal disease), progressive neurological dysfunction (peripheral neuropathy, cerebellar ataxia, CN palsies, dev delay), HLH
- CHS1 gene mutation leading to LYST defect –> cannot transport lysosomes to appropriate sites of action
- Treat acute infections, abx prophylaxis, G-CSF (correct neutropenia), HSCT (however does not prevent neurologic deterioration), IFN gamma
You’re seeing a 33-year-old patient with CVID.
a. Please counsel him on IVIG.
b. What are the genetic mutations associated with CVID?
c. What are the main causes of death?
d. What are the non-infectious complications of CVID?
- Ig replacement is used to replace immunoglobulins which are low in patients with CVID –> there are two forms (IV and SC)
- It helps to reduce infections and need for treatment (including abx, admissions)
- Decreases development of non-infectious complications
- Risks –> blood product (anaphylaxis, infection, hemolysis, TRALI, etc), thromboembolic effects, side effects include headaches (aseptic meningitis), chills, myalgias
Risks
- Blood product
- Explain it is pooled from thousands of donors
- Explain in brief the screening process
- Volunteer donors, screening bloodwork
-Blood placed on hold until donor comes back and repeats tests
- Multiple treatments and nanofiltration to remove viruses
Explain the potential infectious complications: bacterial, viral (HIV, HBV, HCV) and the limitations of screening
- From Uptodate: no IgG product produced with current safety measures has ever been reported to transmit a blood borne disease.
- Adverse effects – rate related
- “Inflammatory symptoms” chills, fever, flushing, myalgias, malaise, nausea and/or vomiting, and headache
- Anaphylactoid reactions or urticaria – usually not-IgE mediated
- Can be manged by slowing down the rate, and if needed, premedication or switch to SCIG
- Adverse effects – other
- Aseptic meningitis - *Screen for history of migraine
- Renal: acute kidney injury, protein or fluid overload (usually in patients with pre-existing kidney disease) – avoid sucrose-containing products
- Heme: hemolysis (rare), neutropenia (rare)
- Thrombotic events (usually in elderly, dehydration, cancer patients)
Genetic mutations:
- usually spontaneous
- most common is TACI - variable penetrance
- Others: ICOS, BAFFR, CD19, CD20
Main causes of death:
- Malignancy and lung disease
What are some of the complications of CVID besides infections
- GI: 20% of patients – IBD, sprue-like disease,
- Resp: bronchiectasis, BO, granulomatous lymphocytic interstitial lung disease (GLILD)
- Liver: dysfunction in 10% - incl nodular regenerative hyperplasia
- Autoimmunity: AIHI, ITP, RA, pernicious anemia
- Malignancy: NHL, stomach ca
You’re seeing an 8-year-old female with a low lymphocyte count.
a. Discuss DDx and approach
b. Investigations
c. She is found to have a low CD3 and CD19 count. CD4 and CD8 are both low. She has normal NK cells and normal RA/RO. She has a low PHA and her TCR V beta has a spike. What is your management of this case?
DDx:
- Primary immunodeficiency –> e.g. humoral or combined immunodeficiency; CVID, DiGeorge, SCID
- Infection (viral eg HIV, flu; bacterial eg TB, typhoid, brucellosis; fungal eg histo; parasitic eg malaria)
- malignancy/neoplasm (e.g. lymphoma)
- malnutrition
- Autoimmune (SLE, RA, Sjogren’s, sarcoidosis, etc)
- Medications (ritux, steroids, chemo, radiation, etc)
- Aplastic anemia, pancytopenia
- Losses –> renal, GI (PLE)
- Idiopathic CD4+ lymphopenia
Hx/physical
- Hx of infections, growth, exposures, ROS
- Birth and pregnancy hx
Invx:
- CBCD, smear, albumin, renal function, IgG/M/A/E, vaccine titres, LSUB, ESR/CRP, HIV, ANA, ENA, urinalysis, ?PHA, ?RA/RO, ?TCR V beta
- NBS –> TRECs
- CXR?
Management:
- Omenn syndrome? Digeorge?
- SCID precautions - avoid all live vaccines, irradiated/CMV negative blood products, PJP prophylaxis (Septra), IVIG replacement
- HLA subtying for patient & siblings
- HSCT (may need pre-stem cell treatment)
You are seeing a 6-month-old male with a history of diarrhea and failure to thrive. He has had 2 episodes of pneumonia and one skin infection.
a. Please provide a history and outline your physical exam and investigations.
b. You find out from your history that he has watery stools and eczema. What is your differential?
DDX:
- Infection
- Congenital IBD
- PID –> CGD, SCID, IPEX, CVID, XLA, Hyper IgM, LRBA/CTLA-4 deficiencies, DOCK8 deficiency, APECED, ALPS, Digeorge, WAS
- CF?
- FPIES
- NEC
DDx - SCID, HIES, Omenn, WAS, DiGeorge, hyper IgM, IPEX, APECED
Prenatal
Pneumonias – documentation
Blood cultures
Vomiting, intake,
Blood work
Rash
THRUSH
7-8 stools a day, watery, no blood, no mucus
BW 3kg, 5kg
Eczema from birth
?Aspiration
Famhx – early childhood deaths, CF??
Exam – lymph nodes tonsils?, dysmorphic features (digeorge), hair – maternal GVHD causes alopecia, Finger nails?
Labs – CBC, T&B cell, IgG,m,a,e, diph, tet, t cell stim, vbeta rep, sweat chloride,
WAS
IPEX
Netherton’s
T-B+NK
T cell stim abn
Diphth 0.08, tet 0.06
HIV DNA
Sweat chl. Normal
Albumin, total
GLUCOSE
IgE
Extended phenotype – All CD4+CD45RA+
Septra 5mg/kg/day
You are seeing a 22-month-old male with recurrent skin abscesses.
a. Please take a history and describe your physical exam
b. Provide a differential diagnosis and outline your investigations
c. Patient is found to have X-linked CGD. Describe your management
DDx:
PID:
* Phagocytic defects
* CGD
* LAD
* Congenital neutropenia
* Cyclic neutropenia
* HIES - ?cold abscesses
* IL-10 and IL-10 receptor deficiency
* Dock8 deficiency
* Chediak-Higashi syndrome*
Non-immunodeficiency:
* IBD/Crohn’s
* CF?
* HIV
* ?Diabetes
* Drug abuse e.g. injections
Immunosuppressive medications
History:
¨ Infectious history: abscesses, sinopulmonary infections, bacteremia, osteomyelitis
¨ Associated symptoms: eczema, periodontal disease, fractures, enterocolitis, hepatic, urinary,
¨ MRSA risk factors: HCP, family members with skin infections, crowding, frequent exposure to antibiotics
¨ FamHx: consanguinity
What is your management?
¨ Septra
¨ Intraconazole
¨ Consider interferon gamma 50 mcg/m2 subcutaneously three times per week
¨ Plan for HSCT
What is the pathophysiology of CGD?
¨ Phagocytes use NADPH to generate reactive oxygen species
¨ Defect in one of the subunits of the phagocyte oxidase (PHOX), part of the secondary granule in neutrophils. 2 membrane (gp91, p22) and 3 cytosolic (p47, p67, p40)
¨ XL – gp91; AR – others
¨ PHOX required for generation of superoxide and killing
You see a 9-month-old male who is toxic looking with fever, rash, hepatosplenomegaly, as well as cervical and inguinal adenopathy.
a. What is your differential diagnosis? What are the diagnostic criteria for HLH?
b. He is found to have fever, cytopenias, splenomegaly, and a very high ferritin. What further investigations may you want to perform?
DDx:
- HLH
- PID –> ALPS, Griscelli, Chediak Higashi, XLP
- Autoimmune –> SLE, KD, sJIA, etc
- Infection/sepsis, toxic shock syndrome
- Liver dysfunction/failure
- Malignancy
- Medication related
Diagnostic criteria:
need 1 of the following 2 criteria:
1. molecular diagnosis consistent with HLH (e.g. PRF mutations, SAP mutations) OR
2. Presence of 5/8:
- Fever
- Splenomegaly
- Cytopenia (affected 2 or more cell lineages –> Hgb, plt, neutrophils)
- Hypertriglyceridemia and/or hypofibrinogenemia
- Hemophagocytosis in the BM, spleen, or LN w/o evidence of malignancy
- Low or absent NK cell cytotoxicity
- Hyperferritenemia
- Elevated soluble CD25
Investigations:
- Bloodwork: liver enzymes, liver function (e.g. INR), ESR/CRP, TG
- Genetic testing?
- Bone marrow biopsy?
- imaging –> AUS +/- CT abdomen
- Blood cultures (r/o sepsis)
- Viral serology e.g. EBV
