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Electrocardiographic changes in recurrent polyserositis (“periodic disease”)
Electrocardiographic Changes in Recurrent Polyserositis ("Periodic Disease")* MARCEL ELIAKIM, M .D .
and
ERNEST N . EIIRENFELD, M .D .
Jerusalem, Israel CLINICAL SYNDROME
of unknown etiology
erythrocyte sedimentation rate . The attacks usually lasted one to four days and appeared at varying intervals of four days to several months . In the interval between attacks the patients felt well and were able to perform their daily work . During an attack the temperature usually rose to 38 to 40'e. . ; the abdomen became tender and rigid ; and chest pain of pleural type caused shallow and rapid respiration . Retrosternal pain was experienced during attacks by one patient before he came under our observation . Many of the patients were subjected to laparotomy because of suspected abdominal disease correctable by surgery . The only finding at laparotoiny was acute congestion of the peritoneum, frequently associated with exudation of round cells and eosinophils . No bacteria were ever found in cultures of the peritoneal exudate . Between attacks the physical findings were absent or scanty ; when present they consisted mainly of a palpable spleen and colloid-bodylike dots in the ocular fundi .
characterized by bouts of fever and A pain in the abdomen and chest has been described in the past fifteen years under various designations .' -5 The underlying pathology of this disorder is a recurrent inflammation of the peritoneum and other serous membranes ; therefore, we have suggested naming it "recurrent polyserositis ." 5 Others have used such names as "benign paroxysmal peritonitis,"' "periodic disease,' 12 "familial Mediterranean fever,"' and "familial recurrent polyserositis ."" The disorder frequently occurs in several members of a family and has been described mainly amongst people of Mediterranean stock. Although the serous membranes are affected primarily, visceral involvement has also been noted in some cases . Amyloidosis with renal failure eventually develops in a small number of patients .' - ' French authors"" 10 have described polyarteritis nodosa in the course of the disease in a few patients . Enlargement of the spleen and liver, heart murmurs (usually systolic, at the apex and Erb's point),''' changes in the eye grounds" and abnormal electroencephalograms"- have been noted in some patients and indicate involvement of internal organs . This paper was prompted by the observation of transitory electrocardiographic changes during attacks in three patients suffering from recurrent polyserositis .
ELECTROCARDIOGRAPHIC OBSERVATIONS
Electrocardiograms were recorded during attacks in twelve patients . Three of these revealed abnormalities which were not present in the intervals between attacks . The remaining nine patients had normal electrocardiograms, four of them also when re-examined between the attacks . Eighteen patients were examined only in the intervals between attacks and all had normal electrocardiograms . Following are the case reports of the three patients with abnormal electrocardiograms .
CLINICAL MATERIAL
Thirty patients with recurrent polyserositis were examined electrocardiographically . The patients were young people aged fifteen to thirty-five years and had suffered from the disease for two to thirty-two years . All of them CASE REPORTS had typical paroxysms of fever, pain in the abdomen, the chest and sometimes joints, CASE 1 . D . R ., an eighteen year old boy, of a accompanied by leucocytosis and increased healthy family, started to suffer from attacks of fever, ' From the Department of Internal Medicine, B, Rothschild Hadassah University Hospital and the Hebrew University Hadassah Medical School, Jerusalem, Israel . APRIL 1961
517
518
Eliakim and Ehrenfeld
L a V V4 J V3 Fro. 1 . Electrocardiograms . A, during attack ; and B, in the r terval between attacks . ('Pop row, Case 1 ; middle, Case 2 ; and bottom, Case 3) . Note changes suggestive of pericarditis on day of attack in Cases I and 2. Case 3 reveals nonspecific T wave changes dining the attack . The electrucardiugrarns arc within normal limits in all eases in the intervals between attacks . abdominal pain and occasional vomiting at the age of sixteen . The attacks lasted for about twenty-four hours and recurred at intervals of lour days to one month . During attacks the leucocyte count would rise as high as 16,000 per cu- mm . and an erythrocyte sedimentation rate of 44/74 mm ., first and second hour respectively (method of 4Vestergren), was recorded . Physical examination revealed no abnormalities except for a grade 2, systolic apical murmur suggesting mitral valvular disease . Albuminuria was not present, An x-ray film of the chest revealed slight bulging of the pulmonary conus . Numerous bacteriologic and biochemical examinations were within normal limits . The electrocardiogram during an attack (Fig. IA, top) revealed a sinus rhythm of 80 per minute, P-Q interval of 0 .14 second, QRS complex 0 .08 second, S-T segment slightly elevated in leads I, aVL and more so in VrV5 . The T waves were not remarkable . In the interval between attacks the electrocardiogram was within normal limits (Fig . 1E, top) . CASE 2 . L . M„ a fourteen year old boy, suffered since the age of ten years from attacks of arthritis
affecting many of the large joints and accompanied by high lever . Lately, abdominal pain accompanied the attacks which were usually of one to four days' duration and appeared at intervals of one to several weeks . A sister of the patient suffered from a similar disorder and died of amyloidosis . Examination of the patient revealed a grade 2, systolic murmur over the apex and pulmonary valve area as well as a palpable spleen and liver . During an attack the affected joints became warm, swollen and tender and the abdomen distended . The leucocytc count rose to about 11,000 per cu . mm . and the erythrocyte sedimentation rate to 50/85 mm ., first and second hour respectively . The urine contained no albumin . The Congo red test was negative . An electroencephalogram performed twelve days after an attack revealed generalized irregularity of background activity, diffuse theta activity and some bursts of slow and sharp waves . Numerous other laboratory examinations were noncontributory . The electrocardiogram during an attack (Fig . 1A, middle) showed sinus rhythm at the rate of 88 per minute, P-Q interval of 0 .16 second, QRS complex of 0 .08 second with RR' peaks in V 1 ; S-T segment THE AMERICAN JOURNAL OF CARDIOLOGY
Electrocardiogram in Recurrent Polyserositis
519
was isoelectric with a straight ascent to the T waves in leads I, n, V s and V s ; in V i-V 4 the S-T segment was deviated upwards and coved ; the T waves were upright but of low voltage in leads i, aVF and peaked and negative in 'V2-VI . Eight days later the electrocardiogram was within normal limits except for low voltage of the QRS complex in the limb leads and shift of the axis to the left (Fig . 1B, middle) .
pericardium may pass unaccompanied by pain or any other sign . It is, therefore, conceivable that pericardial involvement as demonstrated
CASE 3. E . L . was a forty-six year old woman . In 1944 the patient began to suffer from attacks of pain in the chest and abdomen accompanied by fever . Pain in the joints and severe headache occasionally accompanied the attacks . The temperature usually rose to 38°c ., sometimes preceded by a chill . Each attack lasted one to three days and recurred at irregular intervals of three days to several months . Between attacks the patient felt well and worked as a cook . One of her sons, aged twenty-six, suffered from attacks similar to hers. Physical examination of the patient revealed many white dots diffusely distributed in both eye grounds . The heart and lungs were normal ; the liver and spleen were not palpable . During attacks the abdomen became very tender and distended . The white blood countroseto 18,000 per cu . mm . and the sedimentation rate to a maximum of 11.2/123 mm ., first and second hour respectively . On fluoroscopy, limitation of movements of the diaphragmatic leaflets was sometimes observed. Urine analysis was within normal limits . The Congo red test was negative . An electroencephalogram during an attack showed runs of slow activity in the left temporooccipital region ; on another occasion the electroencephalogram was within normal limits . Other laboratory tests were noncontributory . The electrocardiogram during an attack showed sinus rhythm of 82 per minute, P-Q interval of 0 .19 second, QRS complex of 0 .07 second, S-T interval isoelectric in all leads ; T wave flat, diphasic or inverted in the various leads (Fig . lA, bottom) . Between attacks the electrocardiogram was within normal limits (Fig . 1B, bottom) .
As mentioned previously, the sister of the patient in Case 2 died of uremia ; autopsy revealed amyloid infiltration of the myocardium, the valve leaflets and the pericardium . The deposition of amyloid is a dynamic process and may possibly explain the electrocardiographic changes during attacks . Furthermore, it has been pointed out by several authorse •s • 10 that a diffuse perivascular inflammatory reaction may occasionally occur in recurrent polyscrositis . It is possible that such a reaction is of transitory nature in the early stage of the disease and, if affecting the heart, may cause short-lived changes in the electrocardiogram .
by the electrocardiographic changes in Cases 1 and 2 may be more frequent in recurrent polyserositis than hitherto realized . In some cases of recurrent polyserositis, amyloidosis of the myocardium may develop .'
SUMMARY
Thirty patients with recurrent polyserositis were examined electrocardiographically . The electrocardiogram was obtained during an attack in twelve of the patients and in the intervals between attacks in twenty-five patients . Electrocardiographic abnormalities were noted in only three patients examined during attacks . In two of these patients the changes were suggestive of pericarditis and in one they were not specific and were confined to the T wave . In all three patients the electrocardiograms were within normal limits in the intervals between attacks . In none of the remaining patients examined between attacks were abnormalities present in the electrocardiogram .
COMMENTS
The electrocardiographic changes in these patients affected mainly the S-T segments and the T waves . In one patient (Case 3) they were confined to the T wave and were of nonspecific nature ; in the other two patients the changes suggested subepicardial damage . Although definite evidence of a transient inflammatory reaction in the peritoneum and the pleura is available in recurrent polyserositis, no convincing proof of pericardial involvement during the attacks has been offered as yet . Pain of pericardial origin is rarely experienced by these patients . However, it is well known that a transitory inflammatory reaction of the APRIL 1961
REFERENCES 1 . StscAL, S . Benign paroxysmal peritonitis . Ann . Int. Med ., 22 : 1, 19452 . REiMANN, H . A . Periodic disease : probable syn-
drome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia . J . A . M. A ., 136 : 239, 1948. 3 . HELLER, H ., SOHAR, E . and SHERr, 1 . . Familial Mediterranean fever . Arch. Int. Med., 102 : 50, 1958 . 4 . Pairsx, R . J . and NIXON, R. K. Familial recurrent polyserositis, a disease entity. Ann . Int . Med., 51, 1253, 1959 . 5 . RACHMILEWITZ, M., EHRENPELD, E. N . and ELIAKIM, M. Recurrent polyserositis . J. A . M. A ., 171 2355, 1959 .
520
Eliakim and Ehrenfeld
6 . MAMOU, H,
La Maladie Periodique, p . 42. 1956 . Expansion Scicntifiquc Frangaisc I,'expansion ed . 7 . TrQu .Arc, N . A . Periodic disease : a clinicopathological study . As, Jet . Med ., 49 : 885, 1958 . 8 . EURENFLLD, E. N ., ELIAKIM, M . and RACHMILEWITZ, M . Recurrent polyserositis . A report of 55 cases . Am . J . Med . In press . 9 . BDNHAMOU, E ., ALDou, A., DESTAINC, F ., FERRAND, B. and BOINF.AU . N, Periarterite noueuse et maladie pfriodique . Bull . e1 me'm. Sac- reed. hap_ Paris, 70 : 247, 1954 .
10 . Bosoms, H . dique .
Periarterite noueuse et maladie perio-
Tunisie AIed. . 43 : 79, 1955 .
11 . MiCHALL5o , I ., ELLAKrm, M ., EHRENFF.LD . E . N . and RACHMILE'VITZ, M . Fundal changes resembling colloid bodies in recurrent polvserusilis ("periodic disease") . Arch . Ophth ., 62 : 1,
1959 . 12 . ELIAKIM, M . and BENTAI, F. .
Electroencephalographic changes in recurrent polyserositis ("periodic disease") . Arch. Jut . Med. In press .
THE AMERICAN JOURNAL OF CARDIOLOGY
and
ERNEST N . EIIRENFELD, M .D .
Jerusalem, Israel CLINICAL SYNDROME
of unknown etiology
erythrocyte sedimentation rate . The attacks usually lasted one to four days and appeared at varying intervals of four days to several months . In the interval between attacks the patients felt well and were able to perform their daily work . During an attack the temperature usually rose to 38 to 40'e. . ; the abdomen became tender and rigid ; and chest pain of pleural type caused shallow and rapid respiration . Retrosternal pain was experienced during attacks by one patient before he came under our observation . Many of the patients were subjected to laparotomy because of suspected abdominal disease correctable by surgery . The only finding at laparotoiny was acute congestion of the peritoneum, frequently associated with exudation of round cells and eosinophils . No bacteria were ever found in cultures of the peritoneal exudate . Between attacks the physical findings were absent or scanty ; when present they consisted mainly of a palpable spleen and colloid-bodylike dots in the ocular fundi .
characterized by bouts of fever and A pain in the abdomen and chest has been described in the past fifteen years under various designations .' -5 The underlying pathology of this disorder is a recurrent inflammation of the peritoneum and other serous membranes ; therefore, we have suggested naming it "recurrent polyserositis ." 5 Others have used such names as "benign paroxysmal peritonitis,"' "periodic disease,' 12 "familial Mediterranean fever,"' and "familial recurrent polyserositis ."" The disorder frequently occurs in several members of a family and has been described mainly amongst people of Mediterranean stock. Although the serous membranes are affected primarily, visceral involvement has also been noted in some cases . Amyloidosis with renal failure eventually develops in a small number of patients .' - ' French authors"" 10 have described polyarteritis nodosa in the course of the disease in a few patients . Enlargement of the spleen and liver, heart murmurs (usually systolic, at the apex and Erb's point),''' changes in the eye grounds" and abnormal electroencephalograms"- have been noted in some patients and indicate involvement of internal organs . This paper was prompted by the observation of transitory electrocardiographic changes during attacks in three patients suffering from recurrent polyserositis .
ELECTROCARDIOGRAPHIC OBSERVATIONS
Electrocardiograms were recorded during attacks in twelve patients . Three of these revealed abnormalities which were not present in the intervals between attacks . The remaining nine patients had normal electrocardiograms, four of them also when re-examined between the attacks . Eighteen patients were examined only in the intervals between attacks and all had normal electrocardiograms . Following are the case reports of the three patients with abnormal electrocardiograms .
CLINICAL MATERIAL
Thirty patients with recurrent polyserositis were examined electrocardiographically . The patients were young people aged fifteen to thirty-five years and had suffered from the disease for two to thirty-two years . All of them CASE REPORTS had typical paroxysms of fever, pain in the abdomen, the chest and sometimes joints, CASE 1 . D . R ., an eighteen year old boy, of a accompanied by leucocytosis and increased healthy family, started to suffer from attacks of fever, ' From the Department of Internal Medicine, B, Rothschild Hadassah University Hospital and the Hebrew University Hadassah Medical School, Jerusalem, Israel . APRIL 1961
517
518
Eliakim and Ehrenfeld
L a V V4 J V3 Fro. 1 . Electrocardiograms . A, during attack ; and B, in the r terval between attacks . ('Pop row, Case 1 ; middle, Case 2 ; and bottom, Case 3) . Note changes suggestive of pericarditis on day of attack in Cases I and 2. Case 3 reveals nonspecific T wave changes dining the attack . The electrucardiugrarns arc within normal limits in all eases in the intervals between attacks . abdominal pain and occasional vomiting at the age of sixteen . The attacks lasted for about twenty-four hours and recurred at intervals of lour days to one month . During attacks the leucocyte count would rise as high as 16,000 per cu- mm . and an erythrocyte sedimentation rate of 44/74 mm ., first and second hour respectively (method of 4Vestergren), was recorded . Physical examination revealed no abnormalities except for a grade 2, systolic apical murmur suggesting mitral valvular disease . Albuminuria was not present, An x-ray film of the chest revealed slight bulging of the pulmonary conus . Numerous bacteriologic and biochemical examinations were within normal limits . The electrocardiogram during an attack (Fig. IA, top) revealed a sinus rhythm of 80 per minute, P-Q interval of 0 .14 second, QRS complex 0 .08 second, S-T segment slightly elevated in leads I, aVL and more so in VrV5 . The T waves were not remarkable . In the interval between attacks the electrocardiogram was within normal limits (Fig . 1E, top) . CASE 2 . L . M„ a fourteen year old boy, suffered since the age of ten years from attacks of arthritis
affecting many of the large joints and accompanied by high lever . Lately, abdominal pain accompanied the attacks which were usually of one to four days' duration and appeared at intervals of one to several weeks . A sister of the patient suffered from a similar disorder and died of amyloidosis . Examination of the patient revealed a grade 2, systolic murmur over the apex and pulmonary valve area as well as a palpable spleen and liver . During an attack the affected joints became warm, swollen and tender and the abdomen distended . The leucocytc count rose to about 11,000 per cu . mm . and the erythrocyte sedimentation rate to 50/85 mm ., first and second hour respectively . The urine contained no albumin . The Congo red test was negative . An electroencephalogram performed twelve days after an attack revealed generalized irregularity of background activity, diffuse theta activity and some bursts of slow and sharp waves . Numerous other laboratory examinations were noncontributory . The electrocardiogram during an attack (Fig . 1A, middle) showed sinus rhythm at the rate of 88 per minute, P-Q interval of 0 .16 second, QRS complex of 0 .08 second with RR' peaks in V 1 ; S-T segment THE AMERICAN JOURNAL OF CARDIOLOGY
Electrocardiogram in Recurrent Polyserositis
519
was isoelectric with a straight ascent to the T waves in leads I, n, V s and V s ; in V i-V 4 the S-T segment was deviated upwards and coved ; the T waves were upright but of low voltage in leads i, aVF and peaked and negative in 'V2-VI . Eight days later the electrocardiogram was within normal limits except for low voltage of the QRS complex in the limb leads and shift of the axis to the left (Fig . 1B, middle) .
pericardium may pass unaccompanied by pain or any other sign . It is, therefore, conceivable that pericardial involvement as demonstrated
CASE 3. E . L . was a forty-six year old woman . In 1944 the patient began to suffer from attacks of pain in the chest and abdomen accompanied by fever . Pain in the joints and severe headache occasionally accompanied the attacks . The temperature usually rose to 38°c ., sometimes preceded by a chill . Each attack lasted one to three days and recurred at irregular intervals of three days to several months . Between attacks the patient felt well and worked as a cook . One of her sons, aged twenty-six, suffered from attacks similar to hers. Physical examination of the patient revealed many white dots diffusely distributed in both eye grounds . The heart and lungs were normal ; the liver and spleen were not palpable . During attacks the abdomen became very tender and distended . The white blood countroseto 18,000 per cu . mm . and the sedimentation rate to a maximum of 11.2/123 mm ., first and second hour respectively . On fluoroscopy, limitation of movements of the diaphragmatic leaflets was sometimes observed. Urine analysis was within normal limits . The Congo red test was negative . An electroencephalogram during an attack showed runs of slow activity in the left temporooccipital region ; on another occasion the electroencephalogram was within normal limits . Other laboratory tests were noncontributory . The electrocardiogram during an attack showed sinus rhythm of 82 per minute, P-Q interval of 0 .19 second, QRS complex of 0 .07 second, S-T interval isoelectric in all leads ; T wave flat, diphasic or inverted in the various leads (Fig . lA, bottom) . Between attacks the electrocardiogram was within normal limits (Fig . 1B, bottom) .
As mentioned previously, the sister of the patient in Case 2 died of uremia ; autopsy revealed amyloid infiltration of the myocardium, the valve leaflets and the pericardium . The deposition of amyloid is a dynamic process and may possibly explain the electrocardiographic changes during attacks . Furthermore, it has been pointed out by several authorse •s • 10 that a diffuse perivascular inflammatory reaction may occasionally occur in recurrent polyscrositis . It is possible that such a reaction is of transitory nature in the early stage of the disease and, if affecting the heart, may cause short-lived changes in the electrocardiogram .
by the electrocardiographic changes in Cases 1 and 2 may be more frequent in recurrent polyserositis than hitherto realized . In some cases of recurrent polyserositis, amyloidosis of the myocardium may develop .'
SUMMARY
Thirty patients with recurrent polyserositis were examined electrocardiographically . The electrocardiogram was obtained during an attack in twelve of the patients and in the intervals between attacks in twenty-five patients . Electrocardiographic abnormalities were noted in only three patients examined during attacks . In two of these patients the changes were suggestive of pericarditis and in one they were not specific and were confined to the T wave . In all three patients the electrocardiograms were within normal limits in the intervals between attacks . In none of the remaining patients examined between attacks were abnormalities present in the electrocardiogram .
COMMENTS
The electrocardiographic changes in these patients affected mainly the S-T segments and the T waves . In one patient (Case 3) they were confined to the T wave and were of nonspecific nature ; in the other two patients the changes suggested subepicardial damage . Although definite evidence of a transient inflammatory reaction in the peritoneum and the pleura is available in recurrent polyserositis, no convincing proof of pericardial involvement during the attacks has been offered as yet . Pain of pericardial origin is rarely experienced by these patients . However, it is well known that a transitory inflammatory reaction of the APRIL 1961
REFERENCES 1 . StscAL, S . Benign paroxysmal peritonitis . Ann . Int. Med ., 22 : 1, 19452 . REiMANN, H . A . Periodic disease : probable syn-
drome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia . J . A . M. A ., 136 : 239, 1948. 3 . HELLER, H ., SOHAR, E . and SHERr, 1 . . Familial Mediterranean fever . Arch. Int. Med., 102 : 50, 1958 . 4 . Pairsx, R . J . and NIXON, R. K. Familial recurrent polyserositis, a disease entity. Ann . Int . Med., 51, 1253, 1959 . 5 . RACHMILEWITZ, M., EHRENPELD, E. N . and ELIAKIM, M. Recurrent polyserositis . J. A . M. A ., 171 2355, 1959 .
520
Eliakim and Ehrenfeld
6 . MAMOU, H,
La Maladie Periodique, p . 42. 1956 . Expansion Scicntifiquc Frangaisc I,'expansion ed . 7 . TrQu .Arc, N . A . Periodic disease : a clinicopathological study . As, Jet . Med ., 49 : 885, 1958 . 8 . EURENFLLD, E. N ., ELIAKIM, M . and RACHMILEWITZ, M . Recurrent polyserositis . A report of 55 cases . Am . J . Med . In press . 9 . BDNHAMOU, E ., ALDou, A., DESTAINC, F ., FERRAND, B. and BOINF.AU . N, Periarterite noueuse et maladie pfriodique . Bull . e1 me'm. Sac- reed. hap_ Paris, 70 : 247, 1954 .
10 . Bosoms, H . dique .
Periarterite noueuse et maladie perio-
Tunisie AIed. . 43 : 79, 1955 .
11 . MiCHALL5o , I ., ELLAKrm, M ., EHRENFF.LD . E . N . and RACHMILE'VITZ, M . Fundal changes resembling colloid bodies in recurrent polvserusilis ("periodic disease") . Arch . Ophth ., 62 : 1,
1959 . 12 . ELIAKIM, M . and BENTAI, F. .
Electroencephalographic changes in recurrent polyserositis ("periodic disease") . Arch. Jut . Med. In press .
THE AMERICAN JOURNAL OF CARDIOLOGY