AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Hodgkin lymphoma (HL) is an unusual lymphoma that can manifest with constitutional symptoms (eg, fever, weight loss, night sweats) termed B-type symptoms. The periodic fever associated with HL is known as the Pel-Ebstein fever.

The criteria for B-type symptoms include fever (ie, temperature >38°C [>100.4°F]) for 3 consecutive days, weight loss exceeding 10% of body weight in 6 months, and night sweats. Pruritus, previously considered an important systemic symptom, does not by itself have prognostic importance and is not sufficient on its own to classify a patient as possessing B-type symptoms.

Pathophysiology

The pathophysiologic mechanism of the Pel-Ebstein fever is unknown; however, it is presumed to be due to cyclic cytokine release.

Frequency

United States

No reliable objective data are known regarding the occurrence rate of classic Pel-Ebstein fever in a series of patients with HL. Anecdotally, some authorities estimate a 5-10% occurrence rate.

International

US and international rates of Pel-Ebstein fever are not known to differ.

Mortality/Morbidity

• The Pel-Ebstein fever is not an independent cause of either morbidity or mortality, although the high fevers can be quite uncomfortable.
• The episodic hemolysis sometimes associated with Pel-Ebstein fever has been suggested to be due to increased susceptibility of older erythrocytes to temperature-induced hemolysis. Two cases of Pel-Ebstein fever temporally associated with pancytopenia have been reported, which would seem to suggest a cytokine-mediated etiology.

Race

No evidence indicates that Pel-Ebstein fever manifests differently or with different frequencies according to race.

Sex

Pel-Ebstein fever is not known to be sex-linked.

Age

No frequency differences by age group are known.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Pel-Ebstein fever was described by 2 physicians in the late 1800s.
• • Wilhelm Ebstein, a German internist who was a professor of medicine in Göttingen, described a patient with relapsing fever in "Das chronische Rückfallsfieber, eine neue Infektionskrankheit." Berliner klinische Wochenschrift, 1887, 24: 565-8, 837.
  • Pieter Pel was a physician in Amsterdam who noted a similar finding years earlier in "Zur Symptomatologie der sogenannten Pseudo-Leukämie." Berliner klinische Wochenschrift, 1885, 22: 3-7.
• Pel-Ebstein fever has been used as an example of a disease that exists only because it has a name.

Physical

• The diagnosis of Pel-Ebstein fever is made by examining a patient's temperature over several weeks.
• The classic description is of a relapsing, high-grade fever that can reach 40-40.5°C (105-106°F) and has a periodicity of 7-10 days. The fever spikes are abrupt in onset and resolution. The fever spikes overlie a temperature baseline that never quite reaches normal.
• Multiple, evenly spaced Beau lines in the nailbeds have been described as indicative of relapsing fever.

Causes

• The etiology of Pel-Ebstein fever is thought to be cytokine release. Cytokines known to be released by Reed-Sternberg cells include interleukin 13, macrophage colony-stimulating factor, transforming growth factor-alpha, interleukin 10, and the T cell–directed CC chemokine thymus- and activation-regulated chemokine. Monocyte chemotactic protein 1 and interleukin 8 have also been detected at increased levels in HL tissues.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Pancreatic carcinoid tumor

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• In a patient with true Pel-Ebstein fever, the diagnosis is established by the histologic finding of HL or another lymphoma. (Other lymphomas and malignancies may be associated with fevers, but only the fever associated with HL is named Pel-Ebstein.)
• No laboratory tests are particularly useful in persons with Pel-Ebstein fever.
• In rare cases, Pel-Ebstein fever has been associated with episodic hemolysis. In these cases, hemolysis laboratory studies may be helpful in making a diagnosis.

Imaging Studies

• Imaging studies are not useful in the diagnosis of the fever; however, CT scans of the neck, chest, abdomen, and pelvis, as well as PET or gallium scans, can be useful in the diagnosis of the underlying Hodgkin lymphoma.

Procedures

• No diagnostic procedures are particularly useful in persons with Pel-Ebstein fever beyond the biopsy used to diagnose the HL or causative lymphoma.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Therapy for Pel-Ebstein fever involves the following 2 concepts:
• • Standard antipyretic regimens, including aspirin and nonsteroidal anti-inflammatory drugs
  • Most importantly, chemotherapy for the underlying lymphoma
• Pel-Ebstein fever reportedly responds to chemotherapy within as short as 2 days.

Surgical Care

Surgery is not indicated.

Consultations

Consulting a hematologist or oncologist for the management of the underlying HL is mandatory.

Diet

Diet modification is ineffective in the therapy for Pel-Ebstein fever.

Activity

Activity restriction does not play a role in treatment of Pel-Ebstein fever.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Antipyretic therapy and chemotherapy for the underlying lymphoma are the 2 mainstays of medical therapy for Pel-Ebstein fever. Treatment of the underlying lymphoma or Hodgkin lymphoma (HL) is beyond the scope of this discussion (see Hodgkin Disease).

Drug Category: Antipyretic agents

These agents are used to reduce uncomfortable fevers.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• No particular inpatient requirements are indicated for the management of Pel-Ebstein fever.

Further Outpatient Care

• No particular outpatient therapy is warranted.

In/Out Patient Meds

• Antipyretics are a mainstay of therapy, along with chemotherapy for HL.

Complications

• Several reported cases of hemolysis have been associated with Pel-Ebstein fever. Whether the degree of hemolysis is inappropriate for the degree of fever or whether this is merely a temperature-related hemolytic reaction has not been determined. Additionally, 2 cases of cyclic pancytopenia have been reported.

Prognosis

• B-type symptoms are a negative prognostic factor for HL.

Patient Education

• Patients should be educated on the appropriate timing of antipyretic therapy.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The differential diagnosis of relapsing fever is a possible source of malpractice liability.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Colvett KL, Patel D, Smith JK. Multiple Beau''s lines in a patient with fever of unknown origin. South Med J. Dec 1993;86(12):1424-6. [Medline].
• Dankbaar H, Willemze R, Bieger R. Bone marrow disorders in Hodgkin''s disease: cyclic pancytopenia coinciding with Pel-Ebstein fever. Neth J Med. 1983;26(3):74-6. [Medline].
• Good GR, DiNubile MJ. Images in clinical medicine. Cyclic fever in Hodgkin''s disease (Pel- Ebstein fever). N Engl J Med. Feb 16 1995;332(7):436. [Medline].
• Hilson AJ. Pel-Ebstein fever [letter; comment]. N Engl J Med. Jul 6 1995;333(1):66-7. [Medline].
• Koopmans RP, van den Born BJ, Kersten MJ, Hart W. [Clinical reasoning and decision making in practice. A 41-year old with periodic fever of unknown origin]. Ned Tijdschr Geneeskd. Sep 13 2003;147(37):1778-83. [Medline].
• McKenna W, Lampert I, Oakley C, Goldman J. Pel-Ebstein fever coinciding with cyclical haemolytic anaemia and splenomegaly in a patient with Hodgkin''s disease. Scand J Haematol. Nov 1979;23(5):378-80. [Medline].
• Molina Boix M, Ortega Gonzalez G, Garcia Perez B, Perez Gracia A. [Pel-Ebstein fever, hemolytic anemia and Hodgkin''s disease (letter)]. An Med Interna. Jul 1989;6(7):388-9. [Medline].
• Racchi O, Rapezzi D, Ferraris AM, Gaetani GF. Unusual bone marrow relapse of Hodgkin''s disease with typical Pel- Ebstein fever. Ann Hematol. Jul 1996;73(1):39-40. [Medline].
• Reimann HA. Periodic (Pel-Ebstein) fever of lymphomas. Ann Clin Lab Sci. Jan-Feb 1977;7(1):1-5. [Medline].
• Storgaard L, Karle H. Fever and haemolysis in Hodgkin''s diseases. Acta Med Scand. Apr 1975;197(4):311-6. [Medline].
• Talbot TR. Cases from the Osler Medical Service at Johns Hopkins University. Hodgkin''s disease with Pel-Ebstein fevers. Am J Med. Mar 2002;112(4):312-3. [Medline].

Article Last Updated: Jun 26, 2006