autoinflammatory conditions

Question 1

NLRP3

Answer 1

The constellation of periodic fever, hives with cold exposure and bilateral sensorineural hearing loss is concerning for Muckle-Wells syndrome, which is caused by a mutation in a gene encoding the NLPR3 inflammasome.

NLRP3 mutation is associated with cryopyrin-associated periodic syndrome, which is a spectrum of autoinflammatory diseases, usually presenting with urticaria (sometimes triggered by cold) and sensorineural hearing loss.

Question 2

MVK

Answer 2

MVK (mevalonate kinase gene), which is a loss of function mutation leading to mevalonate kinase deficiency, causing the autoinflammatory disease hyper IgD syndrome (HIDS) typically presents with anterior neck lymphadenopathy and fevers. Patients are noted to have elevated levels of IgD.

Fever over a week with months in-between flares.

Ends up with an overproduction of interleukin 1-beta (typical autoinflammatory disease).

3-7 days of attack

Question 3

UBA1

Answer 3

Somatic mutations in UBA1 are associated with VEXAS syndrome, causing a myriad of inflammatory presentation as well as cytopenias in older men.

Question 4

MEFV

Answer 4

Familial Mediterranean Fever (FMF)

Question 5

The three forms of CAPS

Answer 5

Mild form is familial cold urticaria, where a patient develops hives when exposed to cold and potentially a fever.

Moderate form is Muckle-Wells syndrome, characterized by hives, episodic fevers and sensorineural hearing loss.

Severe form is neonatal onset multisystemic inflammatory disease (NOMID) affecting newborns with a severe systemic inflammatory disease which is fatal if untreated.

Question 6

Treatment of CAPS

Answer 6

CAPS all have in common a mutation in the NLRP3 inflammasome. This leads to overproduction of IL-1

Question 7

C282Y

Answer 7

hemochromatosis

Question 8

TNFRSF1A

Answer 8

TRAPS
Attack greater than 7 days. Myalgias and rash, conjunctivitis, periorbital edema, large joints
renal amyloidosis

somehow we don’t use TNFi but prefer IL-1 inhibitors

Question 9

PAPA

Answer 9

continuous attack
hives like have, epihyseal over grwoth, conjunctiviits,uveitisi, vision/hearing loss, hepatospleonmegally

CD2BP1/PSTPIP1

IL-1 inhibitor/ steroids

Question 10

DIRA

Answer 10

almost continuous

pustulosis, pathergy, steril ostemomyelitits, fevers typically absent

deficiency in IL receptor

treat with anakinra

Question 11

DADA2

Answer 11

fever, stroke, or PAN like presentation, livedo reticulatoris,

CECR1 gene

treat with TNFi

Question 12

Mi-2

Answer 12

not associated with malignancy or ILD
severe

Question 13

MDA-5

Answer 13

ulcerations, ILD
poor prognosis

Question 14

anti-TIF-1gamma (p155/140

Answer 14

cancer associated

Question 15

NXP2 (MJ or p14)

Answer 15

associated with cancer in older patients
calcinosis
feeding tube

Question 16

Anti-SAE

Answer 16

no cancer, ILD association, mild myositis

Question 17

Anti-Jo 1

Answer 17

ASA, with ILD

Question 18

PL-12 (alanyl)

Answer 18

ASA, women over 50, ILD, pulmonary HTN

Question 19

Anti-EJ (glcyl)

Answer 19

ASA

Question 20

Anti-OJ

Answer 20

ASA

Question 21

anti-cN1A or anti-NT5C1a

Answer 21

IBM