Familial Auto inflammatory Syndromes (AKA Hereditary Periodic Fever Syndromes.) Rare

Consider when:

Lifelong, Recurrent Inflammatory Episodes, usually without trigger – though sometimes with physical stimulus e.g. cold, stress, menstrual cycle,  usually with Fever +/- Abdominal pain, diarrhoea, rash or arthralgia, high ESR and CRP , usually with a very regular Periodicity, lasting days or weeks– between which they are well.

Genetic basis, no autoimmune phenomena (ANA –ve)

Unfortunately, no diagnostic tests except Genetic testing

Major subtypes

1) Familial Mediterranean Fever(FMF) – Commonest Med origin<20yrs, 1-3 days, 2-4 week periodicity,fever and serositis (abdo, joints, pleura), rash legs and feet, rarely severe myalgia legs, scrotal swelling, aseptic meningitis . Develop AA Amyloid Rx Colchicine

2) Hyper immunoglobulin D Syndrome(HIDS) Western European. 3-5 days, 4-6 week periodicity .Fever 1^st year of life, and frequent in childhood + cervical lymphadenopathy, abdo pain, vomiting +diarrhoea, headache, myalgia, arthralgia, splenomegaly, skin rash. No Rx, good prognosis

3) Tumour Necrosis Factor Receptor – associated Periodic       Syndrome (TRAPS) any ethnic group  3-4 weeks, 2-6 x per year. Age variable. Fever, skin lesions (moving red patch over myalgia), myalgia, arthralgia, abdominal pain, vomiting, eye symptoms.  Develop AA Amyloid. Rx NSAID, Steroids

4) Muckle-Wells Syndrome (MWS)  24-48 hours begins adolescence with fever, abdominal pain, myalgia, rash, conjunctivitis. Develop AA Amyloid .Rx? Anakinra

5) Familial Cold Auto inflammatory Syndrome few hours to few days begins 1^st year of life, triggered by cold. Rash on extremities, spreads to rest of body, arthralgia, conjunctivitis, fever.  AA Amyloid rare. No Rx

6) CINCA and  NOMID (Paeds only)

Differential Diagnosis

<2 years – infection- hidden or recurrent or weird e.g. Whipples, Malaria

>2 years infectious or malignant diagnoses uncommon

In general:

Main differentials are Adult Stills, Juvenile Chronic RA, PFAPA(Periodic Fever, apthous stomatitis, pharyngitis,adenitis), Schnitzler syndrome, Behcets, Chrons, Sarcoid, Extrinsic alveolitis, Humidifier lung, recurrent PEs, psychogenic, factitious.

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