Immunology Flashcards
What is required for the diagnosis of Dermatomyositis?
Characteristic rash, plus three of the following:
- Muscle weakness
- Muscle enzyme elevation (CK, LDH, AST)
- EMG changes ((increased insertional activity, fibrillations, sharp waves)
- Muscle biopsy (focal necrosis and phagocytosis of muscle fibers, fiber regeneration, endomysial proliferation, inflammatory cell infiltrates)
Lab findings in Juvenile Dermatomyositis:
- ANA positive in 80%
- Myositis associated antibodies (non-specific) - what are they?
- Myositis specific antibodies - what are they?
Presence of MAAs such as SSA, SSB, Sm, ribonucleoprotein (RNP), and double-stranded (ds) DNA may increase the likelihood of overlap disease or connective tissue myositis.
anti–Jo-1, anti–Mi-2, anti-p155/140, anti-NXP2, and other myositis-specific autoantibodies help define distinct clinical subsets
In Juvenile Dermatomyocarditis and other rheumatological disorders, antibodies to ______ are often associated with complications with pulmonary interstitial fibrosis and cardiac involvement
Pm/Scl antibodies
What are three specific common long term complications with dermatomyositis?
Vasculitis (including, but uncommonly GI), Lipodystrophy (progressive loss of subcut and visceral fat) and calcinosis
This fever syndrome is associated with a classic rash.
Other clinical findings include scrotal pain caused by inflammation of the tunica vaginalis testis, febrile myalgia, exercise-induced myalgia (particularly common in children), and an association with various forms of vasculitis, including Henoch-Schönlein purpura, in as many as 5% of pediatric patients
FMF
_________ is caused by autosomal recessive mutations in MEFV, a gene encoding a 781 amino acid protein denoted pyrin (Greek for “fever”).
What is the inheritance pattern of this syndrome and what age group does it affect?
FMF - inheritance pattern is autosomal recessive.
Commonly seen affecting ids under the age of 20
Are FMF mutations gain of function or loss of function?
Affect MEFV gene
FMF mutations lead to a gain-of-function activation of caspase-1 and IL-1β–dependent inflammation
What is the incidence of amyloidosis in FMF if left untreated?
Amyloidosis
Serum AA, an acute-phase reactant found at extremely high levels in the blood during FMF attacks, is cleaved to produce a 76–amino acid fragment that misfolds and deposits ectopically, usually in the kidneys, GI tract, spleen, lungs, testes, thyroid, and adrenals.
The most common presenting sign of AA amyloidosis is ______.
proteinuria
The diagnosis is then usually confirmed by rectal or renal biopsy
HIDS, also known as _______ deficiency
HIDS, also known as mevalonate kinase deficiency
HIDS and FMF are both autosomal recessive conditions. What are key differentiating features?
Age?
Symptoms?
Age - HIDS presents at <1yo of life; FMF at <20 yr
Symptoms:
- HIDS: Febrile attacks last 3-7 days, with abdominal pain often accompanied by diarrhea, nausea, and vomiting. Other differentiating cervical lymphadenopathy, diffuse macular rash, aphthous ulcers, headaches, and occasional splenomegaly
- FMF: Febrile attacks last 1-3 days, arthralgia, peritonitis, pleuritis and pericarditis dominate. Classic erypselias rash
In what three fever syndromes is Amyloidosis most common?
FMF - 60% if untreated
TRAPS - 25% if untreated
MWS - 30% if untreated
How is HIDS commonly diagnosed?
- 2 mutations in MVK (approximately 10% of patients with seemingly typical disease have only a single identifiable mutation) OR
- Elevated levels of mevalonate in the urine during acute attacks
Mevalonate kinase - MVK
What age group and what are the duration of attacks in TRAPS?
First decade of life - longer attacks 1-4 weeks as compared to FMF/HIDS
Which syndrome?
Misfolded TNFR1 aggregates intracellularly and leads to constitutive signaling through mitogen-activated protein kinases or nuclear factor (NF)-κB, resulting in the release of proinflammatory cytokines such as IL-6, IL-1β and TNF-α.
TRAPS
Age of onset in Cryopyrin assoc fever syndromes is?
<6mo of age
Which Fever syndrome?
Affects kids <1yo, attacks can be hours to days, some arthraligia but present with aspectic meningitis, deafness, conjunctivitis and can have raised ICP/optic disc oedema, progressive SNHL or visual impairment
NOMID
Factor H deficiency is associated with:
Atypical haemolytic-uremic syndrome
C1 INH deficiency is associated with ______
Hereditary angioedema
Name four common SCID genetic abnormalities?
1) IL2R gamma deficiency
2) RAG1
3) JAK3
4) ADA
Which allergies are kids most likely to outgrow?
Milk, egg, wheat and soya
Aspergillus or fungal infections are more likely to occur in absence of which immune cell?
Most commonly neutrophils
Test for CGD?
Dihydrorhodamine (DHR) test
Stimulate a respiratory burst
Child presents with firmly attached umbilical cord and high neutrophil count?
Leukocyte adhesion defect; often poor healing (leukocytes not allowed outside the circulation)
What is the most common X-linked SCID? (genetic defect
Also has T-, NK-, B+
IL-2 Gamma chain defect
