Pel-Ebstein fever

History

The publications of Pel and Ebstein were, surprisingly, based on only a few cases.

In 1885 Pel published an article in the Berliner Klinische Wochenschrift with the heading of “Zur symptomatologie der sog. Pseudo-leucaemie”. In this article he described 2 patients who had a recurrent fever for rather a long time. There was a fever for about 10-14 days and in between a period of the same length without fever. The patients had a considerably enlarged liver and spleen. During the fever-free periods the patients felt much better and the spleen was smaller. Gradually the patients became sicker and they died. On autopsy of the first patient a much-enlarged liver and spleen was found, but also a remarkable enlargement of the central lymfnodes. This was called at that time “Pseudo-leucaemia”: the macroscopic findings of leukaemia, without the leukocytosis.

The second patient died because of cardiac failure, at the post-mortem was found a big tumour in the chest cavity, which was called a lymfosarcoma. Pel mentioned as synonym of pseudo-leukaemia: Hodgken’sche Krankheit (italics by me), Adenie, progr.mult.Drüsenhypertrophie, malignes Lymphom. Because the type of fever was very similar to that of a chronic typhus abdominalis he presumed that an infectious cause was responsible for the disease.

Later this year this article is widely referred in the “Nederlands Tijdschrift voor Geneeskunde” (general medical journal for the Netherlands: NTvG). In October 1885 Pel published in the NTvG a third case.

In august 1887 W.Ebstein published in the Berliner klinische Wochenschrift (BKW) an article titled “Das chronisches Rückfallfieber, eine neue infectioskrankheit”. Here he described a young man, 19 years old, who had recurrent fevers for 9 months, precisely fever for 14 days after which an intermission of 10-12 days. At examination no cause was found, only an enlarged spleen. The patient was still alive, so there were no post-mortem findings. Ebstein refers to the publication of Pel, agrees that the symptoms and signs are similar but he disagrees about the diagnosis of pseudo-leukaemia. He indicates that the fever of pseudo-leukaemia is more irregular. He proposes to call this new infectious disease: “chronisches Rückfallfieber.

In September Pel reacts in the same journal, in an article titled “Pseudo-leukaemie oder chronisches Rückfallfieber?” He deplores that Ebstein did not read the article about his third case and he indicates that in this case there is a special form of pseudo-leukaemia.

In November 1887 Ebstein publishes in BKW a follow-up on his first article, after the patient had died. At the autopsy an enlarged liver and spleen was found and many enlarged lymfnodes. In this very long article Ebstein discusses the fever with diseases of this kind and he refers often to Pel. He also refers to an article, written in 1870 by Murchison*) wherein he describes this kind of fever. Finally Ebstein sticks to his own opinion that in cases of regular recurrent fever there is question of a separate disease and he sticks to the name he proposed earlier.

As far as the name Pel-Ebstein: I do not know who used this for the first time. In the databank of the NTvG the name is first used in 1918 in an article by Bzn.van Esso titled ”A case of acute Pseudleukaemia, type Pel-Ebstein (chronisches Rückfallfieber)”. The second and up to now last time the name appears in the NTvG is in 1990 in an article about a patient with Aids.

*) Ch.Murchison: Transactions of the pathological society of London vol XXI.page 372: “case of lymphadenoma of the lymphatic system, spleen, liver, lungs, heart, diaphragm, dura mater, etc.” He describes a girl 6 years old who had progressive enlarged lymfnodes since 2 years and who was admitted to the hospital the last 3 weeks before her death. The girl had recurrent fevers for some time; during the fever-free periods she felt better and the lymfnodes decreased in size. She died probably because of compression of the trachea by intrathoracic tumours. At autopsy (also microscopic findings) a massive swelling of all the lymfnodes appeared to be the case without many pathological findings further. Murchinson discusses the cases of this kind that have been published earlier, for the first time by Hodgkin in 1832 (“on some Morbid Appearances of the Absorbent Glands and Spleen” in Med.-Chir. Trans., 1832, Vol.XVII, p.68). Murchinson does not mention fever at all in his discussion.

Pel-Ebstein still important?

We now know that Pel-Ebstein fever, as described by the original authors, as a rather regular intermittent fever is very rare. Rather common are fever periods in cases of (not yet treated) (non)Hodgkin. If a patient has an intermittent fever the diagnosis of (non)Hodgkin must certainly be concluded in the differential diagnosis, also if there are no lymphnodes palpable as yet. That this is difficult sometimes, even in well-known hospitals, shows the case of King Hussein of Jordan:

King Hussein started in February 1997 to have periods of fever. The local doctors couldn’t find a cause and they thought that some kind of viral infection could be responsible for the fever. In the fall he had a routine cheque-up in the Mayo clinic in the USA (he had been treated for carcinoma of the kidney earlier). Because he still had fevers they sought for a cause but they also talked about a viral infection of unknown origin. Only the next year the diagnosis of non-Hodgkin was made. The king did not react well on the chemotherapy and died in February 1999. (These facts I found in: “ Leap of faith, a memoir of an unexpected life, by Queen Noor” 2003)

Mentioning in some medical textbooks

In 2000 I searched the textbooks in the library of our local hospital for Pel-Ebstein fever.

- Harrison 1998: On the subject fever: Fever 3-10 days, typical for Hodgkin and other lymphomas

- Cecil 1996 : In table” fever patterns as diagnostic clues”: periodic fever (Pel-Ebstein phenomenon) with variable cycles. > Hodgkin’s disease

Hegglin 1980 : “wellenformigen Fieber” according to literature with Hodgkin 90% fever, 31% Pel-Ebstein

- Oxford Textbook of medicine 1996: Subject fever: Pel-Ebstein very uncommon. Subject Hodgkin: P-E is considered to be characteristic for Hodgkin but is rarely encountered in practice

- Harvey c.s. 1984: P-E not mentioned

- Dorland dictionary: Gives also fever of Murchinson-Pel-Ebstein, refers to P-E