Scand J Haematol(l979) 23, 378-380 CASE REPORT

Pel-Ebstein Fever Coinciding with Cyclical Haemolytic Anaemia and Splenomegaly

in a Patient with Hodgkin’s Disease

WELW MCKENNA, IRvm LAMPERT, CELU OAKLEY BE JOHN GOLDMAN Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital,

London, England

A 46-year-old man with an aortic valve replacement was investigated for recurrent episodes of fever associated with splenomegaly and haemolytic anaemia. Initially bacterial endocarditis was suspected. At laparotomy he proved to have mixed cel- lularity Hadgkin’s disease confined to the spleen. The undefined mechanism under- lying Pel-Ebstein fever in this patient may also have been the cause1 of simultaneous haemolysis and splenomegaly.

Key words: haemolytic anaemia - Hodgkin’s disease - Pel-Ebstein fever - splenolmegaly

Accepted for publication September 15, 1979

Correspondence to: Dr. W. J. McKenna, Hammersmith Hospital, Ducane Road, London W12, England

In 1887 Pel and Ebstein independently de- scribed relapsing fever in patients with Hodgkin’s disease, a syndrome that now bears their name. In fact a similar pattern of fever was described by Murchison 17 years earlier and the syndrome should, therefore, strictly be designated ‘Murchison- Pel-Ebstein’ fever. More than a century af- ter its first description its cause is essentially unknown.

In 1963 Ranlov & Videbaek described a patient in whom Pel-Ebstein fever coincided with episodes of haemolysis. Their patient did not have splenomegaly. We report here a patient with Pel-Ebstein fever and epi- sodes of haemolysis which coincided with periodic splenomegaly. His diagnosis was complicated by an aortic valve replacement,

which initially focused attention on the pos- sibility of infective endocarditis.

CASE REPORT

A 46-year-old male Saudi teacher had an aortic valve replacement for severe calcific aortic steno- sis in 1969. In Aug 1978 he presented in Jedda with a 3 month history of recurrent pyrexia (38- 39O C). His spleen descended 10 cm below the costal margin. The left dorsalis pedis pulse was absent. The Hb was 85 g/l, WBC 5.3 X 1W/1 and ESR (Westergren 1 h) = 102 mm. Four blood cultures were negative but serum titres to typhoid H and 0 antigens were raised (both 1:1280). Typhoid endocarditis was diagnosed. The patient received oral chloramphenicol for 2 weeks and oral ampicillin for 5 weeks. He became afebrile within 24 h of commencing treatment and spleen size was reduced. After stopping antibiotics, how-

0036-553X/79/100378-03 $02.50/0 @ 1979 Munksgaard, Copenhagen

PEL-EBSTEIN FEVER IN HODGKIN'S DISEASE 379

ever, pyrexia recurred and splenomegaly was again noted. He was then transferred to the Hammersmith Hospital in London. On examina- tion he was afebrile. He had no stigmata of endo- carditis and no lymphadenopathy. The spleen was not now enlarged. He was in sinus rhythm; the prosthetic valve sounds were normal and there was no early diastolic murmur. Investigation showed H b 120 &/1 with normal red cell mor- phology, WBC 4.4 x 109/1 with 60 % neutrophils, 25 % lymphocytes and 12 % monocytes. The ESR was 90 mm. A diagnosis of inadequately treated infective endocarditis was made and the patient was commenced on i.v. penicillin and gentamicin and oral fucidin.

During the fourth week of treatment the pa- tient developed a pyrexia 38-40°C associated with sweats, 10 cm splenomegaly and a drop in Hb of 40 gJ1 over 72 h (Figure 1). The Hb fell to a low of 70 gA and the patient required transfusion. Since the pyrexia and anaemia were felt to be a

I Penicillin I I- 36

Transfusion

4 'f 2 0 u IC JEDDA +HAMMERSMITH

drug reaction, fucidin was replaced by flucloxa- cillin to complete 5 weeks of i.v. antibiotics. The patient remained febrile (38-40° C) for 2% weeks including 6 d following completion of antibiotic therapy. An aortogram showed a well-functioning StamEdwards aortic valve and no evidence of an aortic root abscess. His condition improved spontaneously after treatment with antibiotics and he was discharged; his spleen was impalpable and his only medication was Warfarin. 6 weeks later, however, the patient returned with pyrexia of 39" C; splenomegaly (7 cm) was again noted. The H b was 77 g/l and reticulocytes ranged from 5- 15 % over the subsequent week. The bilirubin was elevated (501 % was conjugated). SGOT and al- kaline phosphatase were minimally raised. Re- peated direct and indirect Coombs' tests were negative, serum haptoglobin was less than 40 mg/ dl (normal = 60-270 mg/dl), plasma Hb was 16 mg/l and urinary Hb, urinary haemosiderin and Schumm's test were negative. There was no evi-

Splenectomy

Transfusion

1

r A HOSPITAL& Figure 1. Recurrent fever coin-

I I I I ciding with recurrent spleno- 0 4 8 12 18 22 megaly and also recurrent haemo-

WEEKS lytic anaemia.

380 W. McKENNA, I. LAMPERT, C. OAKLEY & J. GOLDMAN

dence of haemorrhage. The thrombotest was 20 %, Hb electrophoresis was normal. A bone-marrow showed erythroid and myeloid hyperplasia. The probable diagnosis of lymphoma was made.

Further investigations to rule out bacterial, fungal and protozoal infection were all negative. A diagnostic laparotomy and splenectomy were performed. The spleen was considerably enlarged (550 g) but there were n o abnormal lymph nodes. Histologically the spleen showed multiple deposits of mixed cellularity Hodgkin’s disease with sev- eral areas of necrosis. There were numerous haemosiderin-containing macrophages surrounding the tumour nodules and elsewhere in the red pulp. A wedge biopsy of liver showed extra- medullary haemopoiesis in the sinusoids. Bone marrow trephine showed erythroid and myeloid hyperplasia. The pathological stage was therefore I B although the possibility of unrecognised liver involvement existed. The patient was treated with MOPP (nitrogen mustard, vincristine, procarba- zine, prednisoloae); he has gained his lost weight (9 kg) and has remained completely well at 6 months.

DISCUSSION

Anaemia is present in 30-50 % of patients with Hodgkin’s disease at initial presenta- tion. In patients without splenomegaly or bone marrow involvement it is often un- explained; in some of these patients red cell survival is shortened and red cell destruc- tion in the spleen can be demonstrated and cured by splenectomy even in the absence of Hodgkin’s disease in that organ (Cline & Berlin 1967).

Our patient exemplifies the unusual as- sociation of a cyclical enlargement of the spleen coinciding with a swinging pyrexia and episodes of haemolysis. That all were due to the Hodgkin’s disease is suggested by the negative tests for endocarditis and other causes and the apparent cure of the syndrome by splenectomy and chemother- apy. No autoantibodies were demonstrated.

Although haemolysis due to damage to red cells from the prosthetic aortic valve would have been accelerated by the increased car- diac output associated with fever and anae- mia, the normal red cell morphology and persisting serum haptoglobins suggested that mechanical haemolysis played only a mini- mal role.

Ranlgv & Videbaek (1963) reported a similar patient with Pel-Ebstein fever and cyclical haemolytic anaemia but without splenomegaly. They suggested that the pe- riodic formation of antibodies was the ini- tiating mechanism. This is possible and con- sistent with the known disturbance in im- munological function in Hodgkin’s disease. Our patient, however, had normal immuno- globulins, negative Coombs’ test and no evidence of cold agglutinins or marrow plasmacytosis. The mechanism of the fever, the splenomegaly and the haemolysis re- mains obscure and little can be added to the comment made by Dorothy Reed in 1902 that in Hodgkin’s disease ‘irregular or con- tinuous fever is the rule, attributable to the inflammatory nature of the disease’.

REFERENCES

Cline M J & Berlin N I (1963) Anemia in Hodg kin’s disease. Cancer 16, 526-31.

Murchison C (1870) Case of ‘lymphadenoma’ of lymphatic system, spleen, liver, lungs, heart, diaphragm, dura mater, etc. Trans Pathol SOC London 21, 372-89.

Ranl@v P & Videbaek Aa (1963) Cyclic haemo- lytic anaemia synchronous with Pel-Ebstein fever in a case of Hodgkin’s disease. Acta Med Scand 174, 583-89.

Reed D M (1902) On the pathological changes in Hodgkin’s disease with especial reference to its relation to tuberculosis. Johns Hopkins Hosp Rep 10, 133-96.