IM Flashcards
(78 cards)
Recurrent episodes of swelling without urticaria or pruritus that primarily affects the skin, mucosa of the upper respiratory tract and the gastrointestinal tracts (presenting acute-onset abdominal pain and widespread mucocutaneous edema) following a dental procedure or some type of trauma is suggestive of?
This is suggestive of hereditary angioedema (HAE).
An autosomal-dominant form of C1-esterase inhibitor deficiency that causes bradykinin-mediated angioedema. It can be triggered by trauma, surgery, dental procedures, infections, and drugs.
Gastrointestinal complaints and facial swelling without urticaria and pruritus are typical symptoms for this type of angioedema.
The episodes are usually self-limited and resolve within 2–4 days.
Examples of T-cell mediated immune reactions?
T-cell mediated immune reaction is seen in type 4 hypersensitivity reactions. This is classically a delayed response that takes several days to develop, and includes;
drug reactions,
Stevens-Johnson syndrome,
graft-versus-host reaction, and
multiple sclerosis.
Adverse effects of cyclosporine
Cyclosporine A: is a calcineurin inhibitor that m/c presents with gingival hyperplasia, hirsutism, and hypertension.
All A/Es:
Nephrotoxicity !!!!
Neurotoxicity
Gingival hyperplasia
Hypertrichosis and hirsutism
Diabetogenic effect (particularly after organ transplantation), which can lead to:
Hyperuricemia
Hyperlipidemia
Elevated liver enzymes
Increase in malignancies and infectious diseases (e.g., increase in the risk of squamous cell carcinoma by 50% in patients who are on simultaneous treatment with PUVA during psoriasis treatment)
Hypertension
Hyperkalemia
Tremors
Nausea and diarrhea
Adverse effect of Tacrolimus
Tacrolimus (FK506): is also a calcineurin inhibitor. M/c A/Es hyperlipidemia, anemia, thrombocytopenia, arthralgia, and acne
Other a/es include:
Nephrotoxicity!!!!!: monitor for oliguria
Neurotoxicity!!!!! (more severe compared to cyclosporin)
Hypertension
Diabetogenic effect (more severe compared to cyclosporin A) [7]
Hyperglycemia
Hyperuricemia
Hyperlipidemia
Elevated liver enzymes
Hair loss
Headache
Nausea and diarrhea
Insomnia
Abdominal discomfort
Hyperkalemia
Hypophosphatemia
Hypomagnesemia
Both calcineurin inhibitors (cyclosporine A and tacrolimus) are highly nephrotoxic. They become even more nephrotoxic when combined and should, therefore, never be administered concurrently!
Many side effects of tacrolimus are similar to cyclosporine A, but tacrolimus does not cause ?
gingival hyperplasia or hypertrichosis.
A/Es of Purine analogs (azathioprine, mercaptopurine)
Pancytopenia (leukopenia, macrocytic anemia, thrombocytopenia): exacerbated by interaction with allopurinol, since it inhibits xanthine oxidase, which is responsible for the degradation of 6-mercaptopurine
Hepatotoxicity
Malignancies, including cervical cancer, lymphoma, squamous cell carcinoma, melanoma (rare)
Nausea, vomiting, and dose-related diarrhea
Acute pancreatitis
Other things to note about purine analogs
Azathioprine is the precursor of 6-mercaptopurine, think “Azathiopurine.”
Allopurinol causes toxic accumulation of azathioprine! In cases in which concomitant treatment is unavoidable, a dose reduction of azathioprine is necessary!
A/Es of mTOR inhibitors (sirolimus, everolimus)
M/c A/Es of Sirolimus specifically: hyperlipidemia, anemia, thrombocytopenia, arthralgia, and acne
Pancytopenia!!!!
Insulin resistance
Hyperlipidemia
No nephrotoxicity
Infection (e.g., respiratory or urinary tract)
Peripheral edema
Hypertension
Stomatitis
Note: To remember that sirolimus can cause pancytopenia, think “Sir, don’t forget your pants!”
In contrast to calcineurin inhibitor tacrolimus, mTOR inhibitors are not ___
Nephrotoxic.
Mycophenolate mofetil
Its most common side effects include bone marrow suppression, vomiting, diarrhea, peripheral edema, elevated blood urea nitrogen, and hyperglycemia.
Other a/es include:
Pancytopenia
Infection (e.g., respiratory or urinary tract), especially with CMV
Vomiting and diarrhea
Hyperglycemia
Hypertension
Comparatively low neurotoxicity and nephrotoxicity
Peripheral edema
↑ Blood urea nitrogen
Hypercholesterolemia
Back pain
Cough
Acute graft vs. host disease
occurs after transplantations of lymphocyte-rich organs (e.g., allogeneic hematopoietic stem cell transplantation) and develops within the first 100 days following the procedure. Donor T lymphocytes trigger a type IV hypersensitivity reaction in the host organs, leading to severe organ damage. Skin, liver, and intestine are commonly affected, so patients present with a maculopapular rash, diarrhea, abdominal pain, jaundice, and cholestatic liver dysfunction. Hematopoietic involvement may also be present (anemia, thrombocytopenia, leukocytopenia).
Definitive Dx: Affected organ biopsy
Definitive Tx: Cyclosporine optimization
Engraftment syndrome
occurs during neutrophil recovery following a hematopoietic stem cell transplantation (HSCT) and can manifest with skin rash, hepatic dysfunction, jaundice, and diarrhea. However, it occurs within 3–4 days of engraftment, which happens within 2–4 weeks following HSCT. In addition, it is often associated with features of a capillary leak such as pulmonary edema and encephalopathy.
X-linked (Bruton) agammaglobulinemia
Definition: X-linked recessive defect of Bruton tyrosine kinase (BTK) expressed in B cells that causes a complete deficiency of mature B lymphocytes
Presents as recurrent pyogenic infections (e.g., pneumonia, otitis media), especially with encapsulated bacteria (S. pneumoniae, N. meningitidis, and H. influenzae), hypoplastic lymphoid tissue (e.g., adenoids), low or absent serum immunoglobulins, and low levels of B cells. Affected individuals typically present after 3–6 months of age because of a drop in maternal IgG levels and the resultant waning of passive immunity. Because this condition is X-linked, mainly male individuals are affected.
Vaccine contraindication in XLA (Bruton’s)
Live vaccines (e.g., MMR) are contraindicated in patients with X-linked (Bruton) agammaglobulinemia.
Definitive Dx for XLA (Bruton’s)
Flow cytometry showing:
Absent or low levels of B cells (marked by CD19, CD20, and CD21)
Normal or high T cells
Low immunoglobulins of all classes
Absent lymphoid tissue, i.e., no germinal centers and primary follicles
Definitive Tx for XLA (Bruton’s)
IV immunoglobulins
Prophylactic antibiotics
Selective IgA deficiency
Definition: most common primary immunodeficiency that is characterized by a near or total absence of serum and secretory IgA
Clinical features:
Often asymptomatic
May manifest with sinusitis or respiratory infections (S. pneumoniae, H. influenzae)
Chronic diarrhea, partially due to elevated susceptibility to parasitic infection (e.g. by Giardia lamblia)
Associated with autoimmune diseases (e.g., gluten-sensitive enteropathy, inflammatory bowel disease, immune thrombocytopenia) and atopy
Anaphylactic reaction to products containing IgA (e.g., intravenous immunoglobulin)
Definitive Dx for Selective IgA deficiency
Decreased serum IgA levels (< 7 mg/dL)
Normal IgG and IgM levels
False-positive pregnancy tests
Definitive Tx for selective IgA deficiency
Treatment of active infections
Prophylactic antibiotics
Intravenous infusion of IgA is not recommended because of the risk of anaphylactic reactions (caused by the production of anti-IgA antibodies).
To prevent transfusion reactions, IgA-deficient patients must ?
be given washed blood products without IgA or obtain blood from an IgA-deficient donor.
The Six A’s of selective IgA deficiency:
Asymptomatic,
Airway infections,
Anaphylaxis to IgA-containing products,
Autoimmune diseases,
Atopy
Common variable immunodeficiency (CVID)
Definition: primary immunodeficiency with low serum levels of all immunoglobulins despite phenotypically normal B cells.
Manifests with recurrent pyogenic infections (e.g., pneumonia, otitis media) and hypogammaglobulinemia. However, the typical age of onset for CVID is 20–40 years. In addition, flow cytometry would show subsets of normal B cells and T cells.
Associated with a high risk of lymphoma, gastric cancer, bronchiectasis, and autoimmune disorders (e.g., rheumatoid arthritis, autoimmune hemolytic anemia, immune thrombocytopenia, vitiligo).
Definitive Tx for CVID
Prophylactic antibiotics in patients with recurrent infections
IV immunoglobulins in patients who develop severe and/or invasive infections or recurrent infections despite prophylaxis
Appropriate treatment in patients with atopic manifestations (e.g., bronchodilators)
Routine immunization schedule should be continued.
Definitve Dx for CVID
Quantitative immunoglobulin levels, IgG is ≤ 2 SD of age-appropriate levels. Levels of IgA and IgM may be low.
Flow cytometry shows subsets of normal B and T cells.
