MORNING REPORT

Chari Larsen, MD PGY-3 October 4, 2013

HPI
7yo healthy girl presents to your continuity clinic around February with complaints of fever for >12 days. Has consistently been >38.5 every day on multiple occasions each day. Parents are worried because the fever is taking too long to resolve. Has associated sore throat, fatigue, pallor, periorbital edema, decreased appetite, leg/foot pain, mouth sores, nasal sores, nausea, and episodic epigastric cramping abdominal pain. All of these symptoms started on day 1-2 of the fever and are persisting. She really has not been acting like herself and is pretty grumpy.

Denies any joint swelling, congestion, cough, sneezing, tachypnea, rashes, weight loss, vomiting, diarrhea.

History
PMH: Term birth without complications. Sleep apnea. Likely anxiety. Seasonal allergies. PSH: Tonsillectomy and adenoidectomy Medications: Levsin, peppermint oil, Tylenol and Motrin PRN, Zyrtec PRN Allergies: NKDA SH: Lives with parents and 3 siblings. 2 are adopted and 1 is a full biological sibling. Patient was conceived using a donor egg (patient is unaware of this). She is in 2nd grade. FH: No chronic medical conditions including IBD, IBS, arthritis, autoimmune diseases.

Immunizations: Up to date.
Development: No delays. Doing well in school.

Physical Exam
Weight: 11.97kg; Height: 133.00cm; BP: 94/52, HR: 100, RR: 20, Temp: 99.1 GENERAL: DELANEY appears well and is cooperative with exam. HEENT: Conjunctivae and sclerae clear. PERRL. No synechiae. EOM's intact. Fundoscopic exam normal. Mild periorbital edema. Normal External ears. TMs B/L. No nasal discharge. The right nare has a small, healing septal ulcer. MMM. No oral ulcerations. NECK: No masses or thyromegaly. mild cervical LAD. RESP: clear to auscultatation B/L. Normal respiratory rate and effort, no wheezes or rales. CV: RRR. Normal S1, S2. No significant murmur. No gallop. No rub. No bruits appreciated ABD: Soft Nontender/Non distended. No Hepatosplenomegaly. GENITALIA: deferred. EXTREMITIES: Warm. Good capillary refill. Normal pulses all 4 extremities. No edema. SKIN: no rash. NEUROLOGIC: No focal abnormalities. No adventitious movements. No ataxia. MUSCULOSKELETAL: Full range of motion of all joints without swelling or tenderness.

7yo girl with >12 days of fevers, abdominal pain, leg pain, periorbital edema, pallor, fatigue, & mouth/nasal sores.

More History
Jump ahead to August Family has been in to see you multiple times now for the same complaints. Fevers always last 10-16 days with the same set of associated symptoms. Have kept a fever journal which notes fevers in
November 2012
February 2013 Late March 2013 May 2013 July 2013

August 2013

Differential Diagnosis
Infectious Disease
CMV/EBV Osteomyelitis FUO Colitis Myositis Strep throat Leukemia Lymphoma Tumor NOS Hemolytic anemia

Rheumatology
PFAPA TRAPs FMF JIA Growing pains Bechets disease CRMO

Constipation Gastritis

Psychiatry
Anxiety Malingering School avoidance

Hematology/Oncology

Nephrology
Nephrotic syndrome CKD

Gastroenterology

Celiac disease Cardiology Crohn disease Atypical KD/KD Functional abdominal pain Mesenteric adenitis

Work-up
5/13/13 FEVER WBC 3.01 (3B/37S/48L/12M), HGB 13.6, PLT 128; ANC 1200, ALC 1400; ESR 4 7/13/13 NO FEVER WBC 11.1 (40S/52S/5.6M/2E), HGB 13.5, PLT 290; ESR 0 CMP WNL, UA WNL C4 29, C3 125, EBV & CMV negative, DNAse B <70, ASO <50, RF <15, ANA negative CRP <0.15, IgA 92, TTG 6, Gliadin 9

Periodic Fevers
How many can you name?
Hint there are 8

How are these conditions classified?

Autoinflammatory syndromes
Group of inflammatory conditions caused by dysregulation of the innate immune system.

PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, & Adenitis)

Most common in North America No known genetic association or inheritance pattern Typically starts age 3-5 Episodes occur REGULARLY every 4-6wks and last for up to 5 days (not longer) Is SELF-LIMITED May have (in addition to the things in the name) nausea, vomiting, abdominal pain, and headache. Throat cultures consistently negative

Treatment: no consensus; single dose of steroids fairly effective, tonsillectomy, or cimetidine

Familial Mediterranean Fever (FMF)

Most common hereditary autoinflammatory disease Autosomal recessive, mutation in the MEFV gene Common in Arabic, Turkish, Armenian, and Mediterranean populations Fevers occur every 4-8wks and last for 1-3 days Clinical hallmark is SEROSITIS (peritonitis, pleuritis, synovitis)
Also have erysipelas-like rash on shins and dorsum of feet, monoarthritis, myalgias

Can develop RENAL AMYLOIDOSIS

Treatment: colchicine or Anakinra if colchicine resistentn

TNF-Receptor Associated Periodic Syndrome (TRAPS)

Autosomal dominant, linked to mutation in TNFRSF1A gene that encodes the TNF receptor Age of onset ranges from childhood to several decades of age Episodes last 3-4 WEEKS and occur at IRREGULAR intervals Clinical findings include: migrating erythematous maculopapular rash that spread from trunk to extremities, severe migratory myalgias associated with rash, arthralgias, conjunctivitis, PERIORBITAL EDEMA, and severe abdominal pain

Treatment: steroid provide symptomatic relief but dont diminish the frequent

Hyperimmunoglobulinemia D Syndrome (HIDS)

Rare Genetic mutation in mevalonate kinase gene >90% show symptoms within the 1st year of life Fevers last 4-7 days and occur every 4-8 weeks Clinical features: abdominal pain, vomiting, diarrhea, tender cervical LAD, oral ulcers, arthralgias, large joint symmetric arthritis Have striking elevation of serum IgD and IgA during the fever episodes Treatment: NSAIDs and corticosteroids

Cryoporin Associated Periodic Syndrome (CAPS)

Group of 3 diseases that are on a continuum of severity All associated with genetic mutations involving NLRP3 gene encoding cryopyrin Onset in INFANCY Familial Cold Autoinflammatory Syndrome (FCAS):
Develop fever, chills, and generalized non-pruritic urticarial skin lesions after exposure to cold Symptoms persist up to 24hrs Risk of developing amyloidosis in adulthood

Muckle Wells Syndrome (MWS):

Generalized urticarial rash, arthralgias, myalgias, arthritis, and conjunctivitis
Frequent fever episodes lasting 24-48hrs Progressive NEUROSENSORY HEARING LOSS emerges in adolescence

CAPS cont.
Neonatal Onset Multisystem Inflammatory Disease (NOMID):
Known as CINCA in Europe Nearly clinical features that develop shortly after birth Fever episdoes lasting 24-48hrs several times a week Distinguishing feature: POOR GROWTH AND FTT Clinical features: nearly constant generalized urticarial rash, aseptic meningitis, SNHL, optic nerve atrophy, intellectual disability, deforming arthropathy, conjunctivitis, episcleritis, uveitis, papilloedema, LAD, HSM Poor long-term prognosis with high morbidity and mortality

PFAPA
Onset Duration Frequency Key Features 2-5yrs 3-5 days 4-6 weeks All in the name <10yrs

FMF
3yrs

TRAPS

FCAS
<6mo <24hr Cold exposure Urticarial rash, chills, severe arthralgias, conjunctivitis

MWS/NOMID
Infnacy-6mo 24-48hrs/ constant Very frequent to constant Urticarial rash, hearing loss, severe limp pain (optic neuritis, chronic meningitis) Autosomal dominant Northern European/All CIAS1/cryopyrin Anti-IL1 agents 6mo

HIDS

1-3 days 4-8 weeks Serositis, erysipelas-like rash, amyloidosis, oligoarthritis Autosomal recessive Armenian, Arab, Turkish, Italian, Jewish MEFV, Pyrin Colchicine

Days weeks Irregular intervals Muscle pain w/ overlying erythema, periorbital edema, large joint arthritis Autosomal dominant All

4-7 days 4-6 weeks Diarrhea, maculopapular rash, cervical LAD, High IgD

Inheritance Ethnicity

Random All

Autosomal dominant European

Autosomal recessive French, Dutch, European MVK/mevalonic kinase NSAIDs, steroids

Gene Involved Treatment

None identified Cimetidine, Steroids, tonsillectomy

TNFRSFIA Steroids, Anti-TNF agents

CIAS1/cryopyrin Anti-IL1 agents

References
Goldsmith, DP. Periodic Fever Syndromes. Pediatrics in Review. Vol. 70, No. 5. Pg e34e41. May 2009. A Residents Guide to Pediatric Rheumatology. 2011 Revised Edition. The Hospital for Sick Children. Pages 41-46.