Prolonged, recurrent and periodic fever — formative SAQs

SAQ 1 (10 marks)

A 3-year-old girl has had high fever every 5 weeks for the last year. Each episode starts abruptly, lasts 4 days, and is accompanied by a sore throat, mouth ulcers and tender enlarged cervical nodes. Between episodes she is entirely well and growing normally. During a documented attack her CRP is 96 mg/L; two weeks later, when she is well, it is 4 mg/L. [2] [3] [4]

1. State the most likely diagnosis and the pattern of fever it represents. (2) [1] [2]
2. Give four clinical features that distinguish this syndrome from the hereditary periodic fevers. (4) [3] [4] [5]
3. Outline the management, including how to abort an attack and the role of tonsillectomy. (4) [3] [6]

Model answer — SAQ 1

(1) Diagnosis and pattern (2). The most likely diagnosis is PFAPA syndrome (periodic fever with pharyngitis, aphthous stomatitis and cervical adenitis). It represents periodic fever — the subset of recurrent fever in which attacks recur at predictable, stereotyped (clockwork) intervals, in this case every 5 weeks. The rise of CRP to 96 mg/L during the attack and its fall to 4 mg/L when well is a PFAPA signature. [1] [2] [3]

(2) Distinguishing features (4). Four discriminating features: onset before 5 years with the classic tetrad of fever, pharyngitis, aphthous stomatitis and cervical adenitis; short attacks of 3 to 6 days (FMF is shorter at 1 to 3 days, TRAPS is far longer at 1 to 3 weeks); clockwork 3-to-8-week intervals; and complete wellness with normal growth and normalising inflammatory markers between attacks, which the hereditary fevers (with serositis, periorbital oedema, vaccination-triggered rash or a 21-day neutropenic cycle) do not share. [3] [4] [5] [8]

(3) Management (4). Reassure the family that PFAPA resolves spontaneously, typically by adolescence, with no long-term sequelae. Abort each attack with a single oral dose of prednisolone 1 to 2 mg per kg at onset, which ends most attacks within hours, though it may shorten the interval to the next episode. For frequent or disruptive attacks, trial cimetidine prophylaxis. Tonsillectomy is supported by three randomised trials and is reserved for severe, refractory disease after multidisciplinary discussion — not first-line, because the syndrome resolves regardless. [3] [6]

SAQ 2 (10 marks)

A 5-year-old boy of Turkish heritage has recurrent 2-day attacks of fever with severe abdominal pain and a swollen, painful ankle, occurring at irregular intervals over 18 months. His father had "recurrent appendicitis" removed at age 14 with a histologically normal appendix. There are no periorbital features and no migratory rash. [5] [7]

1. What is the most likely diagnosis, and which clinical criteria support it? (3) [5] [7]
2. Explain the pathophysiology in one paragraph and name the key long-term complication of untreated disease. (3) [5] [7]
3. Outline the treatment and the single most important reason not to simply observe. (4) [5] [7]

Model answer — SAQ 2

(1) Diagnosis and criteria (3). The most likely diagnosis is familial Mediterranean fever (FMF): short 1-to-3-day attacks of fever with serositis (peritonitis mimicking an acute abdomen, and monoarthritis) in a child of Mediterranean ancestry, with a family history consistent with recurrent serositis mislabelled as appendicitis. The Livneh clinical criteria support the diagnosis, and confirmation is by MEFV genetic testing. The father's histologically normal appendix after "recurrent appendicitis" is a classic FMF clue. [5] [7]

(2) Pathophysiology and complication (3). FMF is a monogenic autoinflammatory disease: gain-of-function MEFV mutation drives constitutive innate-immune and inflammasome activation, with surges of interleukin-1-beta, interleukin-18 and interleukin-6 that produce self-limited attacks of fever and serositis with no infection and no autoantibodies. The key long-term complication of untreated disease is AA amyloidosis, which causes renal failure. [5] [7]

(3) Treatment and rationale (4). Start lifelong colchicine, the disease-specific therapy. The single most important reason not to simply observe is that colchicine prevents not only the attacks but the development of AA amyloidosis and renal failure — this is one of the few paediatric treatments that changes long-term survival. Screen the family and ensure adherence, because the outcome depends on consistent colchicine. Contrast with PFAPA, which is benign and self-resolving and never causes amyloidosis. [5] [7]