Periodic Fevers/Autoinflammatory Syndromes Flashcards
TRAPs
Mutation: TNFRSF1A on chromosome 12p13
Genetics: Autosomal Dominant
Symptoms: Episodic fever and inflammation with serosal, synovial, and cutaneous manifestations
Distinguished by: Long attacks (1-4 weeks), Myalgia under the rash caused by inflammation of underlying fascia
Labs: Serum amyloid A, CRP and complements elevated during flares (may also be elevated in between suggesting a baseline level of inflammatory activity)
Treatment: Infrequent- steroids, Enbrel for more severe disease, INFLIXIMAB is bad, Il-1 may be even better
FMF
Mutation: MEFV on chromosome 16 p
Genetics: Gain of function resulting in increased IL-beta activation
Symptoms: Inflammation of peritoneum, pleura, joints or skin, attacks last 12-72 hours ; Abd pains range from mild discomfort to mimic appendicitis; constipation, arthalgia, muscle pain is classic feature
Labs: CRP, SSA, complement, commonly elevated. if they are elevated between attacks this predisposes to amyloidosis, regularly screen microalbumin
Treatment: Colchicine; IL blockade for those who do not tolerate colchicine
Familial cold autoinflammatory syndrome
Gene: NLRP3 (cyropryin), gain of function leads to constitutive activation of the inflammasome
Sx: Short (<24 hours) self limited episodes of fever, rash (all over body not just cold exposed), and arthralgia precipitated by generalized exposure to cold
Other sx: Conjunctivitis, muscle pain, sweating, drowsiness, HA, extreme thirst, nausea common
Labs: Leukocytosis and elevated APR with episodes
AMYloidosis is rare
Muckle Wells
Fever, urticarial rash, limb pain, and joint swelling, conjunctivitis
Sensorineural hearing loss in 70 percent
Amyloidosis in 25 %
Labs: APR may be elevated with episodes or nearly constantly in severely affected
NOMID/Cinca
- Most severe phenotype
- Symptoms present at or near birth
- Fever can be intermittent, mild or absent
- Urticaria like non pruritic rash
- MSK: Arthalgias and transient swelling to gross deformities of joints and severe bone pain and loss of motion
- Prematurity
- Neurological: increased ICP, progressive cognitive impairment, chronic aseptic meningitis, cerebral ventricular dilitation, cerebral atrophy, spastic diplegia, epilepsy, Macrocephaly causing frontal bossing and saddle nose, hearing loss
- Ocular: uveitis/blindness
- Amyloidosis
Labs: Elevated APR, eosinophilia, hypergamm, no autoantibodies
TX; IL1 inhibition, may need higher doses, NSAIDS and prednisone may offer temp clinical relief
HIDS
Gene: Mevalonic kinase on Chromosome 12 leading to reduced MVK activity—> excessive substrate–> Def in nonsterol isoprenoids
When: Early childhood
How often: 3-7 days , usually separated by 1-2 months
Sx: Chills, fever, HA, abd pain, N/V, poly non destructive arthritis, widespread painful red macules (NOT migratory like TRAPs), oral and vaginal aphthous ulcers, LAD, splenomegaly
- Pleurisy and amyloidosis is rare
Labs: Elevated IgD but can be normal, elevated IgA, elevated APF during and sometimes in between attacks, Elevated urine mevalonic acid during
Triggers: stress, surgery, trauma, infectionss
Tx: may respond to colchine, steroids, IVIG, cyclosporine, simvastatin, enbrel and anakinra
Mevalonic aciduria
Complete mevalonic kinase def
Sx: Dev delays, hematologic abnl, dysmorphic, HSM
- Develop periodic crises with fever, rash and arthralgia
PFAPA
- Febrile episodes every 28 days like clockwork
- Last 5 days
- Malaise, chills, fatigue, aphthous stomatitis, pharyngitis, cervical adenitis
- May have mild arthralgia, abdominal pain, headache
Labs: elevated WBC, APR, CRP higher on days 2-4 than day 1; mild elevations in IgG, IgM, IgA, and maybe IgD - Diagnosis of exclusion
- NSAIDS may alleviate fever in some
- Colchicine may be effective at preventing recurrences
- Steroids may shorten interval between episodes
- Cimetidine may help prevent recurrences
- T&A may eliminate attacks
- Anakinra has been used to treat flares
SAPHO
Synovitis, ACNE, Pustolosis, Hyperostosis, Osteomyelitis
Spectrum of autoinflammatory bone disease
CRMO
- Localized bone pain +/- fever
- Worse at night
- Insidious
- Tenderness, warmth and swelling may or may not be present
- Common sites: Metaphyseal regions of long bones, clavicle, vertebral bodies, pelvis
- Most common extra-osseous manifestation is pustular rash on palms and soles
Tx: NSAIDs then anti TNF, bisphosphonates
Unicentric Castleman’s
- Asymptomatic usually
- Comes to light when a moderately large LN is noted
- Most lesions in mediastinum or lung
- Systemic symptoms are rare
- Tx is resection or if location is not feasible, debunking with ritux or Actemra
Multicentric Castleman’s
- Systemic disease with fever, LAD, HSM, pulmonary symptoms, edema, ascites
- Skin findings: rash, hemangiomata, pemphigus
- Sclerotic bone lesions
- Multi organ failure
Treatment
HHV-8 negative without organ failure–> Actemra or ritux
Organ failure–> Combo ritiux and etoposide
HHV-8 positive–> ganciclovir and rituximab (+ etoposide for more aggressive disease)
Diseases associated with castlemans
AIHA, ITP, Acquired Factor VIII def
Also associated with HHV-8, HIV, Poems, malignancy
Treatment for EM
- Leg elevation, rest and compression aid
- Treat underlying disease
- NSAIDS as first line
- Potassium iodide for patients requiring rapid resolution
- Patients with severe, debilitating symptoms, use short course of systemic steroids
- For recalcitrant disease, use dapsone, colchicine, and plaquenil
Majeed Syndrome
Gene: LPIN2
Sx: Triad of early on set CRMO, congenital dyserythropoetic anemia, and a neutrophilic dermatosis (consistent with sweet syndrome)
Treatment: IL 1b blockade
