Fever – Cyclic

Fever – Cyclic: Excerpt from In A Page: Pediatric Signs and Symptoms

Cyclic or periodic fever is an unexplained fever that recurs after fever-free periods at almost predictably fixed intervals. True cyclic fever is rather uncommon in childhood; it should be differentiated from recurrent fever, which refers to fever prone to relapse at unpredictable and irregular intervals. Often, infections that recur with some regularity are misinterpreted as periodic fever. Thorough interviewing may identify a new source of infectious exposure, such as starting day care.

Differential Diagnosis

• PFAPA, or Marshall syndrome
  –Periodic fever (usually high, 104°F [40°C]), aphthous stomatitis, pharyngitis, and adenitis
  –Most common diagnosis for true cyclic fever, usually in children <5 years
  –Recurs every 3–4 weeks
• Cyclic neutropenia
  –Periodic fever, average cycle of 21 days
  –Pharyngitis, mouth ulcers, and lymphadenopathy are also noted
  –May not be associated with infection
• Infectious diseases
  –Relapsing fever due to Borrelia recurrentis,
  relapses every 10–14 days
  –EBV may occur at 6–8 week intervals
• Familial Mediterranean fever
  –Brief attacks of fever and serositis
  –Autosomal recessive disease
  –Sephardic Jews, Arabs, Turks, and Armenians commonly affected
  –50% have onset before 10 years of age
  –May occur in regular 7–28-day intervals
  –Amyloidosis is a possible complication
• Hyper-IgD and periodic fever syndrome (HIDS)
  –High fevers, abdominal pain, cervical lymphadenopathy, sometimes diarrhea and arthritis, in early infancy
  –Autosomal recessive, most patients from Western Europe (French, Dutch)
  –Cycles may be regular every 14–28 days
  • TNF-receptor-associated periodic syndrome (TRAPS) or Hibernian fever
    –Fever, myalgias with migratory pattern, conjunctivitis and rash
    –Autosomal dominant
    –first described in Irish/Scottish individuals but other ethnic groups involved
    –Amyloidosis is a possible complication (25% of untreated individuals)
  • Familial cold autoinflammatory syndrome or familial cold urticaria
    –Rash, fever, arthralgia, and conjunctivitis
    –Precipitated by exposure to cold
  • Factitious fever

  Workup and Diagnosis

  • History
    –Age of onset, duration of episodes, duration of symptom-free periods, associated symptoms (pharyngitis, aphthous ulcers)
    –Lymphadenopathy, abdominal pain
    –Family history of cyclic fever, ethnicity
    –Exposure to ticks (woods, camping), travel history
  • Physical exam (during fever episode)
    –Mouth ulcers, pharyngitis, lymphadenitis, conjunctivitis
    –Abdominal tenderness, hepatosplenomegaly
    –Arthritis, rash
    –Pericardial friction, pleurisy
  • Physical exam (during fever-free interval)
    –Growth parameters
    –Neurologic exam (ataxia, retardation)
    –Heart murmur
    –Hepatosplenomegaly, lymphadenopathy
  • CBC with differential, diagnostic for cyclic neutropenia
  • Immunoglobulins IgA and IgD (elevated in HIDS)
  • Dark-field microscopy examination of wet peripheral blood for Borrelia recurrentis
  • Familial Mediterranean fever
    –Major and minor diagnostic criteria are available
    –Confirmed by gene analysis
  • Low levels of serum type 1 TNF receptor in TRAPS
  • Documentation of fever in the office should exclude factitious fever

  Treatment

  • PFAPA
    –Single dose prednisone with the onset of symptoms
    –Prophylactic cimetidine and tonsillectomy have been tried to prevent recurrences
  • Cyclic neutropenia
    –Life-long therapy with GCSF decreases risk of infection
  • Familial Mediterranean fever
    –Daily colchicine to prevent attacks and amyloidosis
  • Hyper-IgD
    –Prednisone and colchicine have been used
    –Even without treatment, attacks decrease with age
  • TRAPS
    –Prednisone and etanercept have been reported to be effective
  >

Book Source Details

• Book Title: In A Page: Pediatric Signs and Symptoms
• Author(s): Jonathan E. Teitelbaum, Kathleen O. Deantonis, Scott Kahan
• Year of Publication: 2007
• Copyright Details: In A Page: Pediatric Signs and Symptoms, Copyright © 2007 Lippincott Williams & Wilkins.

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: In A Page: Pediatric Signs and Symptoms Authors: Jonathan E. Teitelbaum, Kathleen O. Deantonis, Scott Kahan Publisher: Lippincott Williams & Wilkins Copyright: 2007 ISBN: 1-4051-0427-9

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