A 9-year-old female came to clinic for a second opinion for continued fevers. She had a 3 month history of episodes of fever up to 103° F. that would last 2-4 days, almost always associated with respiratory symptoms. These episodes originally occurred every 2-3 weeks, but she had an episode one week ago and this week has a similar episode. The current episode is also accompanied by moderate generalized headache and muscle aches. The fevers and other symptoms are well controlled with antipyretics. She is kept out of school because of the fevers and the parents are concerned. The patient has been diagnosed with otitis media and streptococcal pharyngitis clinically. The referring physician was worried because now the patient had headaches along with the fever and thought that maybe she had a periodic fever. Laboratory testing including a complete blood count, electrolytes, rapid streptococcal test, Monospot, urinalysis and chest radiograph were negative. The past medical history shows several episodes of otitis media, and influenza 2 years ago. There have been no hospitalizations or unusual infections. The social history shows that the patient had been home schooled until this year, and lives with 2 older brothers and her parents. There was no travel history, or exposure to people in the military, institutional settings or who were homeless. She drinks city water. The family history reveals migraine headaches that begin in childhood. Her older brother began his at 9-10 years. There was no history of other family members with unusual infectious diseases, problems with fever, or autoimmune diseases other than diabetes in overweight individuals. The family was of northern European descent. An extensive review of systems was negative.
The pertinent physical exam shows a slightly tired female with a temperature of 101° F. The rest of her vital signs are normal and the growth charts reveal normal growth including a 2 pound weight gain since a health supervision visit 5 months ago. HEENT examination showed copious clear rhinorrhea, erythematous pharynx without exudates, and shoddy anterior cervical adenopathy. She had mild tenderness of the head without photophobia or phonophobia. Her lungs were clear and her musculoskeletal examination revealed generalized mild myositis. The rest of her examination was negative. The diagnosis of recurrent fevers most consistent with recurrent viral infections was made, given the fever pattern. The current illness was most consistent with influenza that was currently circulating in the community. As the child had not been in a school-type setting before, viral infections were the most likely cause and this was explained to the family. The parents continued to be anxious about the fevers but were somewhat relieved. The pediatrician developed a plan with the family and local physician to monitor the patient, gather additional symptom data and reassess the patient in a month, with the caveat that if other more serious symptoms developed then the patient would be evaluated at that time and possibly additional testing completed.
Fevers that are perceived by patients, families and health care providers as not following a “normal” pattern bother everyone. Patients and families may have different expectations than healthcare providers about the actual temperature measurement, duration of the fever, and other assorted factors such as where the temperature was taken, the instrument used and whether antipyretic medication had been used. Luckily for most patients, fever, even true recurrent fevers, are often self-limited and have good prognoses.
Fever patterns include:
- Recurrent fever
- Multiple episodes that occur at inconsistent intervals involving multiple organ systems, fever is one component
- Multiple episodes that occur at inconsistent intervals involving a single organ system
- Single episode where signs, including fever, wax and wane
- Prolonged fever
- Single episode where the fever is longer than expected for the clinical diagnosis (for example, viral syndrome lasting > 10 days)
- Single episode where fever initially was a major symptom and then becomes low grade or is only believed to be a problem by the family.
- Fever of Unknown Origin
- Single episode of more than 3 weeks duration where fever (>38.3) occurs on most days. After 1 week of evaluation diagnosis must also be uncertain.
- Periodic fever
- Multiple recurring episodes that occur with regular periodicity or inconsistently, where fever is main feature and where other signs/symptoms are consistent and predictable. Duration of symptoms is days to weeks. Respiratory symptoms are not present.
Patients with true periodic fevers develop a more predictable pattern of fever and illness overtime. Therefore it can be difficult early in the course of the illnesses to know if this is the first presentation of the periodic fever. Periodic fevers often will have an abrupt onset and cessation with fever being the main feature, and there are no respiratory symptoms. Each episode is basically identical with regards to symptoms and their course throughout the episode. The patient is also well between the episodes, and the episodes may occur with a regular periodicity or be inconsistent with their timing. The family history may show family members with similar symptoms or autoimmune illnesses. Periodic fevers also are more common in certain groups genetically:
- Blau syndrome
- Cause – autosomal dominant, chromosome 16
- Fever with arthritis, iritis, and skin rash
- Cyclic neutropenia
- Cause – enzyme defect, autosomal dominant, chromosome 19
- Fevers, pharyngitis, lymphadenopathy and mouth ulcers
- Familial Mediterranean Fever
- Cause – protein defect, autosomal recessive, chromosome 16
- Fever and pain (especially abdominal, pleura, pericardium, scrotum, joints, muscle)
- FCAS/FCUS syndrome
- Familial cold autoinflammatory syndrome/familial cold urticaria syndrome
- Cause – autosomal dominant , chromosome 1
- Fever, arthralgia and rash
- Hyperimmunoglobulinemia D and periodic fever syndrome
- Cause – enzyme defect, autosomal recessive, chromosome 12
- Fever, abdominal pain, joint pain, diarrhea, hepatosplenomegaly, lymphadenopathy, and skin lesions
- Muckle-Wells syndrome
- Cause – autosomal dominant, chromosome 1
- Fever, amyloidosis, deafness, and urticaria
- NOMIC/CINCA syndrome
- Neonatal-onset multisystem inflammatory disease/chronic infantile neurologic cutaneous and articular syndrome
- Cause – autosomal dominant, chromosome 1
- Fever, arthropahy, meningitis, rash
- PFAPA syndrome
- Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy
- Cause unknown
- PAPA syndrome
- Pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome
- Cause – autosomal dominant, chromsome 15
- Tumor necrosis factor receptor-associated periodic syndrome
- Cause – protein defect, autosomal recessive, chromosome 12
- Fever, abdominal pain, painful skin lesions and myalgia
Questions for Further Discussion
1. What is the purpose of laboratory testing in fever syndromes?
2. What laboratory testing would you do for recurrent fevers, prolonged fevers or a fever of unknown origin?
- Age: School Ager
To Learn More
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Padeh S. Periodic fever syndromes.
Pediatr Clin North Am. 2005 Apr;52(2):577-609, vii.
Long SS. Distinguishing among prolonged, recurrent, and periodic fever syndromes: approach of a pediatric infectious diseases subspecialist.
Pediatr Clin North Am. 2005 Jun;52(3):811-35, vii.
Online Mendelian Inheritance in Man. Blau Syndreme.
Available from the Internet at http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=186580 (rev. 6/2/2009, cited 2/18/2010).
Goldfinger, SE. PAPA Syndrome. Merck Manual.
Available from the Internet at http://www.merck.com/mmpe/sec19/ch297/ch297f.html (rev. 1/2009, cited 2/18/2010).
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
2. Essential and accurate information about the patients’ is gathered.
3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
4. Patient management plans are developed and carried out.
5. Patients and their families are counseled and educated.
7. All medical and invasive procedures considered essential for the area of practice are competently performed.
8. Health care services aimed at preventing health problems or maintaining health are provided.
9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
19. The health professional works effectively with others as a member or leader of a health care team or other professional group.
23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital