150
ESOPHAGEAL VARICES IN FELTY’S SYNDROME A CASE REPORT AND REVIEW OF THE LITERATURE RAYMOND W. KLOFKORN, JAMES C. STEIGERWALD, DAVlD M. MILLS, and CHARLEY J. SMYTH A case of upper gastrointestinal tract hemorrhage secondary to esophageal varices in a patient with Felty’s syndrome prompted a review of the pathogenesis and treatment of this condition. Six previously reported cases of this association were found. The clinical picture is that of long-standing rheumatoid arthritis with severe articular and extraarticular manifestations including splenomegaly , depression of the blood elements, mild liver function abnormalities, portal hypertension without cirrhosis or portal vein obstruction, an elevated splenic blood flow, and a reduction in portal hypertension by simple splenectomy. The presence of portal hypertension with varices may be another indication for splenectomy in patients with Felty’s syndrome.
Felty’s syndrome is recognized as the association of splenomegaly, leukopenia, and rheumatoid arthritis.
The rheumatoid arthritis usually is far advanced, rheumatoid factor is present, and other extraarticular rnanifestations such as fever, weight loss, skin ulceration and pigmentation, lymphadenopathy, anemia, thrombocytopenia, and Sjogren’s syndrome are common. Severe recurrent bacterial infections presumably due to the low granulocyte count, hemolytic anemia secondary to sequestration and destruction of red blood cells in the spleen, and severe hemorrhage associated with thrombocytopenia have been considered indications for therapeutic splenectorny in the past. Recent experience with a patient with Felty’s syndrome who required splenectomy because of upper gastrointestinal tract hemorrhage from esophageal varices prompted a review of the pathogenesis and treatment of this unusual complication.
CASE REPORT From the University of Colorado Medical Center, Denver, Colorado. Raymond W. Klokorn, CDR, MC, USN: Fellow in Rheumatic Diseases, University of Colorado Medical Center, presently on the Rheumatology Staff of the Naval Regional Medical Center, San Diego, California; James C. Steigerwald, M.D.: Assistant Professor of Medicine, University of Colorado Medical Center; David M. Mills, M.D.: Assistant Professor of Medicine and Acting Head, Division of Rheumatic Diseases, University of Colorado Medical Center; Charley J. Smyth, M.D.: Professor of Medicine and Head, Arthritis Rehabilitation Unit, General Rose Hospital, Denver, Colorado. Address reprint requests to Raymond W. Klofkorn, M.D., Naval Regional Medical Center, San Diego, California 92134. Submitted for publication May 19, 1975; accepted October 10. 1975.
Arthritis and Rheumatism, Vol. 19, No. 2 (March-April 1976)
KS, a 48-year-old female with Felty’s syndrome, was admitted to Colorado General Hospital after emesis of approximately 1 pint of bright red blood 5 hours earlier. O n the previous day she had developed fever, malaise, nausea, and diarrhea. There was no history of previous hematemesis, abdominal pain, food intolerance, dysphagia, alcohol comsumption, or liver disease. Five years previously, however, aspirin had been discontinued because of asymptomatic melena. N o x-ray studies were done. She had developed rheumatoid arthritis 24 years earlier with involvement of the hands and feet, marked morning stiffness, rheumatoid nodules, and a positive serum rheumatoid factor. Nine years later splenomegaly, white blood count of 2,500 cells/rnma, and thrombocytopenia of 100,OOO plate-
151
lets/mm3 were noted. Two years before admission she developed septic arthritis of the left ankle due t o Staphylococcus aureus which had responded to cephalosporins. At that time the white blood count was 1,100 cells/mm3 and a bone marrow examination showed a relative lack of mature granulocytes. Past medical treatment had consisted of a single unsuccessful course of gold therapy during the second year of her disease, of salicylates which were discontinued 5 years before, and of corticosteroids which had been used for the past 17 years in prednisone-equivalent doses of 5-20 mg per day. At the time of admission she was receiving prednisone, 7.5 mg daily, acetaminophen, 1,200 mg daily, and ferrous sulfate, 300 mg daily. She had had multiple orthopedic reconstructive procedures in the previous 10 years. Two years before she had been found to have erosion of the odontoid process with 10 m m of C1-C2 subluxation but no associated neurologic symptoms or findings. Physical findings on this admission included a chronically ill appearance, temperature 4OoC, blood pressure 100/60 mmHg, pulse rate 140/minute, and pale skin and mucous membranes. The liver was not palpable and had a percussion span of 8 cm; the spleen was palpable to the level of the umbilicus. Rectal examination showed black stool with a 4+ guaiac reaction. The skin showed n o discoloration, ulcers,
spider angiomata, or abnormal venous patterns. Rheumatoid nodules were present on both elbows and the medial aspect of the left ankle. The joints showed changes typical of advanced rheumatoid arthritis and evidence of her surgical procedures. There was no active joint inflammation. The white blood count was 1,300 cells/mm3 with 6% neutrophils and 94% lymphocytes; platelets 108,000/mm3; hemoglobin 10.9 g%; prothrombin time 16 seconds (31% of normal control); fibrinogen 404 mg%; Westergren sedimentation rate 56 mm/hour; positive serum latex rheumatoid factor; speckled positive antinuclear antibody; normal urinalysis; total serum protein 6.0 g%; albumin 3.4 g%; y-globulin 1.7 g%; total bilirubin 0.4 mg%; SGOT 29 IU/l; SGPT 17 lU/l; LDH I18 IU/l; alkaline phosphatase 7.0 Bodanski units; BSP 12.5% retention at 45 minutes; serum iron 65 mg%; and iron binding capacity 329 mg%. The chest x-ray was normal. After gastric lavage using iced saline and transfusion of 4 U of fresh whole blood, no further bleeding occurred. Barium contrast x-rays of the upper gastrointestinal tract showed several large esophageal varices; the stomach and duodenum were normal. On the third hospital day an abscess became evident on the inner aspect of the left thigh and was surgically drained of 300 m l of gross pus which grew E coli on culture. Intramuscular gentamycin and oral erythromycin were given and warm compresses were applied t o the abscess area. Percutaneous liver biopsy showed scattered mild fatty metamorphosis which was felt to be consistent with chronic corticosteroid use. Celiac and selective splenic arteriography showed a strikingly enlarged splenic artery (Figure I), an enlarged coiled splenic vein, a patent portal vein, and large esophageal varices (Figure 2). A liver and spleen scan showed a normal liver size and a massive spleen two and one-half times the size of the liver. Bone marrow biopsy showed a granulocytic: erythrocytic ratio of 1 : 3, normal erythrocytic series, normal megakaryocytes, arrest of the granulocytic series at the metamyelocyte stage, and trace iron with the Prussian blue stain. Splenectomy was done 30 days after her acute hemorrhage. The spleen weighed 1,140 g and measured 250 by 150 by 55 mm. The liver was normal in size but was studded with multiple I-mm nodules. Direct portal vein pressure measurements before and after removal of the spleen were 39 and 18 cm H,O respectively. Needle biopsy of the liver was obtained under direct vision. Histologically the spleen showed evidence of a recent infarction. The liver tissue again had scattered mild fatty changes. Following surgery the leukocyte count increased to 6,100 cells/mms with 63% neutrophils. The abscess healed slowly but completely and there has been no further bleeding from the gastrointestinal tract. Barium contrast studies of the esophagus 3 months and 9 months after surgery showed a marked diminution in the size of the varices. The SGOT, LDH, and alkaline phosphatase levels remain slightly elevated.
REVIEW Fig 1. Selective splenic arteriogram with enlarged splenic artery supplying the enlarged spleen.
Six previously reported cases documenting the association of Felty's syndrome and esophageal Urices were found in the medical literature (1-6). The pertinent
I52
K L O F K O R N ET AL
significant hemorrhage from their varices and I patient died from hemorrhage. The splenic artery was specifically noted to be enlarged and elongated in 2 cases and the portal vein was specifically noted to be patent in 4. Portal hypertension was documented in 5 patients either by measurement of splenic pulp pressure or direct portal vein pressure. Liver tissue from all 7 patients had been obtained by percutaneous needle biopsy, by surgical biopsy, or both. Mild portal tract fibrosis or infiltration with lymphocytes or plasma cells was present in 6 patients. One patient showed significant lobular fibrosis and 1 had only mild fatty metamorphosis. Five patients in this group underwent splenectomy and 1 had an associated splenorenal shunt. Two operated patients died, 1 of a gram-negative septicemia 2 weeks after the operation and the other 6 months later with a pontine hemorrhage. Three patients presenting with variceal hemorrhage had no further bleeding after splenectomy. One patient who did not have splenectomy at the time of laporotomy to oversew the esophageal varices died of massive variceal hemor-
Fig 2. The venous phase ofthe splenic arteriogram showing the enlarged coiled splenic vein, the patent portal vein, and esophageal varices.
clinical features of these 6 cases and the single case reported above are summarized in Table 1. The sex and age distribution and the duration of rheumatoid arthritis are similar to those previously reported in Felty's syndrome (7). All patients had leukopenia and thrombocytopenia documented except 1 for whom the platelet count was not reported. The presence of rheumatoid factor was noted in 6 patients, whereas the presence of antinuclear antibody was mentioned in 3. Blood tests reflecting liver function were abnormal in 5, incomplete in 1 and not mentioned in a seventh patient. The findings relative to the liver, spleen, and portal system, as well as the results of surgical treatment, are detailed in Table 2. The liver was enlarged by examination in 4 patients, normal in size in 1, and not mentioned in 2. Gross inspection of the liver revealed fine nodularity in 3 cases. The spleen was enweight at larged in either by examinationOr by splenectomy or autopsy. Four patients in this group had
Fig 3. Artist's diagram showing the abnormal venous stmctures in Figure 2 .
FELTY'S SYNDROME
153
Table 1. Clinical Features Patient Source Age/Sex Duration RA (years) Duration Felty's (years) WBC/mm3 Platelets IDl/mm3 Hemoglobin ( 9 % ) Rheumatoid factor ANA Bilirubin (mg%) SCOT (normal value) SGPT (normal value) Alkaline phosphatase (normal value) BSP retention (%at45 minutes)
* Not
I
2
3
4
5
6
7
Present case 48/F 24 12 I300 I08 10.9 Strongly positive Positive 0.4 29 (6-2 I ) 17 (5-35) 7 .O (1.0-5.5) 12.5
Blendis ( I , 2) 50/ M 12 2 1700 99 9.4 Positive I : I024 Positive 0.5 50 IU ~ 4 0 ) NR
Ritland ( 3 ) 65/F 21 6 I800 50
Ritland ( 3 ) 64/F 16 NR* 3000 88 13.2 Positive
Barnes (4 38/F 10 4 I000 38 10.4 Strongly positive Positive NR NR
Ellman (5 66/F 6 NK 2500 NK 7.0 Positive
Blendis ( 6 ) 74/F 20 NR I800 80 7.1 Positive I :256 NR I .o NR
35 KA (3-1 3) 9
11.1
Positive NR 0.8 20 (5-17) 13 (4-17) 19 (10-45) 8
NR 0.5 39 (5-17) 17
(4-1 7 ) 39 (10-45) 8
NR "Parenchynial Liver Disease"
NR
NR
NR
NR
NR
NR
reported.
rhage 3 days postoperatively. Liver function remained stable in 2 patients and showed slight deterioration in 1 patient after splenectomy.
DISCUSSION The mechanism of portal hypertension in this group of patients has not been clarified. Several studies have shown that increased total blood flow through the splenic artery in patients with splenomegaly from various causes, including Felty's syndrome, leads to elevated portal vein pressures (1,2,8-10) and, in one report, was shown to be the major contributor to portal hypertension (2). However 9 of 16 patients described in this latter report had evidence of mildly elevated hepatic presinusoidal resistance. Blendis et uf ( 6 ) , in investigating intrahepatic obstruction to portal blood flow in a similar group of patients, took liver biopsies and found small hepatic nodules, reticulum fiber hyperplasia, minimal hepatic cell abnormalities, and round cell infiltration of the portal tracts. Some but not all of the central veins appeared to be narrowed by the nodules. The authors emphasized that these changes could not always be appreciated in tissue obtained by needle biopsy and that liver tissue obtained by wedge section was desirable for study. These changes appear to be identical to those described by Sama et a1 (10) as noncirrhotic portal fibrosis of unknown cause. Obstruction of the portal vein has not been noted
in patients with Felty's syndrome and was specifically not present in 4 of the reviewed cases. Thus portal vein obstruction would not seem to contribute to the portal hypertension. The occurrence of esophageal varices is no doubt due to the portal hypertension seen in these cases and probably reflects the chronicity of the process. The mode of treatment in these patients needs to be evaluated further. Four of these patients had simple splenectomy; 1 died soon after surgery with an infection but none had recurrent hemorrhage during their followup period. One patient with splenectomy and a splenorenal shunt has also done well. In analyzing 28 operated cases of bleeding esophageal varices due to noncirrhotic portal fibrosis (none had rheumatoid arthritis), Sama et a1 noted that 3 of 25 cases treated with portal-systemic shunt procedures had recurrent hemorrhage from varices, whereas 1 of the 3 patients treated with simple splenectomy had recurrent hemorrhage (10). Simple splenectomy in the present case led to an immediate drop in portal pressure and apparent protection against variceal bleeding, even though the varices did not completely recede after 9 months. Reynolds has noted that esophageal varices often do not disappear even after portal-systemic shunt procedures (1 I). More intensive study of this subgroup of Felty's syndrome is obviously needed before firm conclusions can be made about the etiology of portal hypertension and the most beneficial form of treatment. However the
KLOFKORN ET AL Table 2. Portal System-Results
2
1
Patient
3
of Surgery
5
4
7
6
Varices Variceal hemorrhage Spleen size
Yes Yes
Yes No
Yes Yes
Yes No
Yes Yes
Yes No
Yes Yes
1140 g
1500 g
450 g
I248 g
570 g
650 g
Liver size
8-cm span
4 cm
5 cm below RCM NR
4 cm below LCM 4 cm below RCM Not examined
NR*
“Enlarged”
NR
Nodular
8 cm below RCM Smooth
Lobular fibrosis; Portal tract inportal tract infiltration with filtration with lymphocytes lymphocytes and plasma cells
“Some portal tract fibrosis without other features of cirrhosis”
Portal tract fibrosis and infiltration with lymphocpes
NR Patent Splenic pulp: 41 cm H,O
NR Patent Splenic pulp: 37 cm H,O
NR NR “Elevated”
NR NR NR
Diffuse fine nodulation, condensed reticulin trabeculae, round cell infiltration NR NR NR
Splenectomy, splenorenal shunt N o bleeding, liver function stable
N o surgery
Splenectomy
Splenectomy
Varices oversewn
No follow-up available
N o bleeding at N o bleeding, de- Died 3 days after 10 months after terioration in laporotomy with splenectomy liver function, massive variceal hemorrhage died 6 months after splenectomy with pontine hemorrhage
below RCM Finely nodular
Gross appearance Finely nodular of liver Liver biopsy Mild fatty Minimal portal metamorphosis tract fibrosis
Splenic artery Portal vein Portal pressure
Enlarged Patent Direct: 39 cm H,O
Treatment
Splenectomy
Results of treatment
Portal pressure Died with 18 cm H,O, n o septicemia 2 bleeding, liver weeks after function stable splenectomy
Enlarged Patent Splenic pulp?: 20 mm Hg 27 mm Hg Splenectomy
* Not reported.
t Two separate studies. presence of hemorrhage from esophageal varices, and perhaps the presence of uncomplicated portal hypertension, should be considered another possible indication for splenectomy in Felty’s syndrome.
ACKNOWLEDGMENT The authors are indebted to Mr. Robert J. Greaves, Medical Illustrator, and to the Medical Photography Laboratory of the Naval Regional Medical Center, San Diego, for the diagram and photographs.
REFERENCES Blendis LM, Ansell ID, Jones KL, et al: Liver in Felty’s syndrome. Br Med J 1:131-135, 1970 Blendis LM, Banks DC, Ramboer C, et al: Spleen blood flow and splanchnic haemodynarnics in blood dyscrasia and other splenomegalies. Clin Sci 38:73-84, 1970 Ritland S: Cirrhosis of the liver in Felty’s syndrome. Scand J Rheumatol 2:29-32, 1973
4. Barnes C G , Turnbull AL, Vernon-Roberts B: Felty’s syndrome. Ann Rheum Dis 30359-374, 1971 5. Ellman P, Cudkowicz L, Elwood JS: Therapy of Felty’s syndrome. Ann Rheum Dis 14:84-89, 1955 6. Blendis LM, Parkinson MC, Shilkin KB, et al: Nodular regenerative hyperplasia of the liver in Felty’s syndrome. Q J Med 169:25-32, 1974 7. Decker JL: Extra-articular rheumatoid disease, Arthritis and Allied Conditions. Eighth edition. Edited by J L Hollander, DJ McCarty. Philadelphia, Lea & Febiger, 1972, pp 360-363 8. Williams R, Parsonson A, Somers K, et al: Portal hypertension in idiopathic tropical splenomegaly. Lancet 11329-333, 1966 9. Williams R, Condon RE, Williams HS, et al: Splenic blood flow in cirrhosis and portal hypertension. Clin Sci 34:441-452, 1968 10. Sama SK, Bhargava MD, Nath NG, et al: Non-cirrhotic portal fibrosis. Am J Med 51:160-169, 1971 I I . Reynolds TB: Promises! Promises! Hemodynamics and portal-systemic shunt. N Engl J Med 2901484-1485,1974
ESOPHAGEAL VARICES IN FELTY’S SYNDROME A CASE REPORT AND REVIEW OF THE LITERATURE RAYMOND W. KLOFKORN, JAMES C. STEIGERWALD, DAVlD M. MILLS, and CHARLEY J. SMYTH A case of upper gastrointestinal tract hemorrhage secondary to esophageal varices in a patient with Felty’s syndrome prompted a review of the pathogenesis and treatment of this condition. Six previously reported cases of this association were found. The clinical picture is that of long-standing rheumatoid arthritis with severe articular and extraarticular manifestations including splenomegaly , depression of the blood elements, mild liver function abnormalities, portal hypertension without cirrhosis or portal vein obstruction, an elevated splenic blood flow, and a reduction in portal hypertension by simple splenectomy. The presence of portal hypertension with varices may be another indication for splenectomy in patients with Felty’s syndrome.
Felty’s syndrome is recognized as the association of splenomegaly, leukopenia, and rheumatoid arthritis.
The rheumatoid arthritis usually is far advanced, rheumatoid factor is present, and other extraarticular rnanifestations such as fever, weight loss, skin ulceration and pigmentation, lymphadenopathy, anemia, thrombocytopenia, and Sjogren’s syndrome are common. Severe recurrent bacterial infections presumably due to the low granulocyte count, hemolytic anemia secondary to sequestration and destruction of red blood cells in the spleen, and severe hemorrhage associated with thrombocytopenia have been considered indications for therapeutic splenectorny in the past. Recent experience with a patient with Felty’s syndrome who required splenectomy because of upper gastrointestinal tract hemorrhage from esophageal varices prompted a review of the pathogenesis and treatment of this unusual complication.
CASE REPORT From the University of Colorado Medical Center, Denver, Colorado. Raymond W. Klokorn, CDR, MC, USN: Fellow in Rheumatic Diseases, University of Colorado Medical Center, presently on the Rheumatology Staff of the Naval Regional Medical Center, San Diego, California; James C. Steigerwald, M.D.: Assistant Professor of Medicine, University of Colorado Medical Center; David M. Mills, M.D.: Assistant Professor of Medicine and Acting Head, Division of Rheumatic Diseases, University of Colorado Medical Center; Charley J. Smyth, M.D.: Professor of Medicine and Head, Arthritis Rehabilitation Unit, General Rose Hospital, Denver, Colorado. Address reprint requests to Raymond W. Klofkorn, M.D., Naval Regional Medical Center, San Diego, California 92134. Submitted for publication May 19, 1975; accepted October 10. 1975.
Arthritis and Rheumatism, Vol. 19, No. 2 (March-April 1976)
KS, a 48-year-old female with Felty’s syndrome, was admitted to Colorado General Hospital after emesis of approximately 1 pint of bright red blood 5 hours earlier. O n the previous day she had developed fever, malaise, nausea, and diarrhea. There was no history of previous hematemesis, abdominal pain, food intolerance, dysphagia, alcohol comsumption, or liver disease. Five years previously, however, aspirin had been discontinued because of asymptomatic melena. N o x-ray studies were done. She had developed rheumatoid arthritis 24 years earlier with involvement of the hands and feet, marked morning stiffness, rheumatoid nodules, and a positive serum rheumatoid factor. Nine years later splenomegaly, white blood count of 2,500 cells/rnma, and thrombocytopenia of 100,OOO plate-
151
lets/mm3 were noted. Two years before admission she developed septic arthritis of the left ankle due t o Staphylococcus aureus which had responded to cephalosporins. At that time the white blood count was 1,100 cells/mm3 and a bone marrow examination showed a relative lack of mature granulocytes. Past medical treatment had consisted of a single unsuccessful course of gold therapy during the second year of her disease, of salicylates which were discontinued 5 years before, and of corticosteroids which had been used for the past 17 years in prednisone-equivalent doses of 5-20 mg per day. At the time of admission she was receiving prednisone, 7.5 mg daily, acetaminophen, 1,200 mg daily, and ferrous sulfate, 300 mg daily. She had had multiple orthopedic reconstructive procedures in the previous 10 years. Two years before she had been found to have erosion of the odontoid process with 10 m m of C1-C2 subluxation but no associated neurologic symptoms or findings. Physical findings on this admission included a chronically ill appearance, temperature 4OoC, blood pressure 100/60 mmHg, pulse rate 140/minute, and pale skin and mucous membranes. The liver was not palpable and had a percussion span of 8 cm; the spleen was palpable to the level of the umbilicus. Rectal examination showed black stool with a 4+ guaiac reaction. The skin showed n o discoloration, ulcers,
spider angiomata, or abnormal venous patterns. Rheumatoid nodules were present on both elbows and the medial aspect of the left ankle. The joints showed changes typical of advanced rheumatoid arthritis and evidence of her surgical procedures. There was no active joint inflammation. The white blood count was 1,300 cells/mm3 with 6% neutrophils and 94% lymphocytes; platelets 108,000/mm3; hemoglobin 10.9 g%; prothrombin time 16 seconds (31% of normal control); fibrinogen 404 mg%; Westergren sedimentation rate 56 mm/hour; positive serum latex rheumatoid factor; speckled positive antinuclear antibody; normal urinalysis; total serum protein 6.0 g%; albumin 3.4 g%; y-globulin 1.7 g%; total bilirubin 0.4 mg%; SGOT 29 IU/l; SGPT 17 lU/l; LDH I18 IU/l; alkaline phosphatase 7.0 Bodanski units; BSP 12.5% retention at 45 minutes; serum iron 65 mg%; and iron binding capacity 329 mg%. The chest x-ray was normal. After gastric lavage using iced saline and transfusion of 4 U of fresh whole blood, no further bleeding occurred. Barium contrast x-rays of the upper gastrointestinal tract showed several large esophageal varices; the stomach and duodenum were normal. On the third hospital day an abscess became evident on the inner aspect of the left thigh and was surgically drained of 300 m l of gross pus which grew E coli on culture. Intramuscular gentamycin and oral erythromycin were given and warm compresses were applied t o the abscess area. Percutaneous liver biopsy showed scattered mild fatty metamorphosis which was felt to be consistent with chronic corticosteroid use. Celiac and selective splenic arteriography showed a strikingly enlarged splenic artery (Figure I), an enlarged coiled splenic vein, a patent portal vein, and large esophageal varices (Figure 2). A liver and spleen scan showed a normal liver size and a massive spleen two and one-half times the size of the liver. Bone marrow biopsy showed a granulocytic: erythrocytic ratio of 1 : 3, normal erythrocytic series, normal megakaryocytes, arrest of the granulocytic series at the metamyelocyte stage, and trace iron with the Prussian blue stain. Splenectomy was done 30 days after her acute hemorrhage. The spleen weighed 1,140 g and measured 250 by 150 by 55 mm. The liver was normal in size but was studded with multiple I-mm nodules. Direct portal vein pressure measurements before and after removal of the spleen were 39 and 18 cm H,O respectively. Needle biopsy of the liver was obtained under direct vision. Histologically the spleen showed evidence of a recent infarction. The liver tissue again had scattered mild fatty changes. Following surgery the leukocyte count increased to 6,100 cells/mms with 63% neutrophils. The abscess healed slowly but completely and there has been no further bleeding from the gastrointestinal tract. Barium contrast studies of the esophagus 3 months and 9 months after surgery showed a marked diminution in the size of the varices. The SGOT, LDH, and alkaline phosphatase levels remain slightly elevated.
REVIEW Fig 1. Selective splenic arteriogram with enlarged splenic artery supplying the enlarged spleen.
Six previously reported cases documenting the association of Felty's syndrome and esophageal Urices were found in the medical literature (1-6). The pertinent
I52
K L O F K O R N ET AL
significant hemorrhage from their varices and I patient died from hemorrhage. The splenic artery was specifically noted to be enlarged and elongated in 2 cases and the portal vein was specifically noted to be patent in 4. Portal hypertension was documented in 5 patients either by measurement of splenic pulp pressure or direct portal vein pressure. Liver tissue from all 7 patients had been obtained by percutaneous needle biopsy, by surgical biopsy, or both. Mild portal tract fibrosis or infiltration with lymphocytes or plasma cells was present in 6 patients. One patient showed significant lobular fibrosis and 1 had only mild fatty metamorphosis. Five patients in this group underwent splenectomy and 1 had an associated splenorenal shunt. Two operated patients died, 1 of a gram-negative septicemia 2 weeks after the operation and the other 6 months later with a pontine hemorrhage. Three patients presenting with variceal hemorrhage had no further bleeding after splenectomy. One patient who did not have splenectomy at the time of laporotomy to oversew the esophageal varices died of massive variceal hemor-
Fig 2. The venous phase ofthe splenic arteriogram showing the enlarged coiled splenic vein, the patent portal vein, and esophageal varices.
clinical features of these 6 cases and the single case reported above are summarized in Table 1. The sex and age distribution and the duration of rheumatoid arthritis are similar to those previously reported in Felty's syndrome (7). All patients had leukopenia and thrombocytopenia documented except 1 for whom the platelet count was not reported. The presence of rheumatoid factor was noted in 6 patients, whereas the presence of antinuclear antibody was mentioned in 3. Blood tests reflecting liver function were abnormal in 5, incomplete in 1 and not mentioned in a seventh patient. The findings relative to the liver, spleen, and portal system, as well as the results of surgical treatment, are detailed in Table 2. The liver was enlarged by examination in 4 patients, normal in size in 1, and not mentioned in 2. Gross inspection of the liver revealed fine nodularity in 3 cases. The spleen was enweight at larged in either by examinationOr by splenectomy or autopsy. Four patients in this group had
Fig 3. Artist's diagram showing the abnormal venous stmctures in Figure 2 .
FELTY'S SYNDROME
153
Table 1. Clinical Features Patient Source Age/Sex Duration RA (years) Duration Felty's (years) WBC/mm3 Platelets IDl/mm3 Hemoglobin ( 9 % ) Rheumatoid factor ANA Bilirubin (mg%) SCOT (normal value) SGPT (normal value) Alkaline phosphatase (normal value) BSP retention (%at45 minutes)
* Not
I
2
3
4
5
6
7
Present case 48/F 24 12 I300 I08 10.9 Strongly positive Positive 0.4 29 (6-2 I ) 17 (5-35) 7 .O (1.0-5.5) 12.5
Blendis ( I , 2) 50/ M 12 2 1700 99 9.4 Positive I : I024 Positive 0.5 50 IU ~ 4 0 ) NR
Ritland ( 3 ) 65/F 21 6 I800 50
Ritland ( 3 ) 64/F 16 NR* 3000 88 13.2 Positive
Barnes (4 38/F 10 4 I000 38 10.4 Strongly positive Positive NR NR
Ellman (5 66/F 6 NK 2500 NK 7.0 Positive
Blendis ( 6 ) 74/F 20 NR I800 80 7.1 Positive I :256 NR I .o NR
35 KA (3-1 3) 9
11.1
Positive NR 0.8 20 (5-17) 13 (4-17) 19 (10-45) 8
NR 0.5 39 (5-17) 17
(4-1 7 ) 39 (10-45) 8
NR "Parenchynial Liver Disease"
NR
NR
NR
NR
NR
NR
reported.
rhage 3 days postoperatively. Liver function remained stable in 2 patients and showed slight deterioration in 1 patient after splenectomy.
DISCUSSION The mechanism of portal hypertension in this group of patients has not been clarified. Several studies have shown that increased total blood flow through the splenic artery in patients with splenomegaly from various causes, including Felty's syndrome, leads to elevated portal vein pressures (1,2,8-10) and, in one report, was shown to be the major contributor to portal hypertension (2). However 9 of 16 patients described in this latter report had evidence of mildly elevated hepatic presinusoidal resistance. Blendis et uf ( 6 ) , in investigating intrahepatic obstruction to portal blood flow in a similar group of patients, took liver biopsies and found small hepatic nodules, reticulum fiber hyperplasia, minimal hepatic cell abnormalities, and round cell infiltration of the portal tracts. Some but not all of the central veins appeared to be narrowed by the nodules. The authors emphasized that these changes could not always be appreciated in tissue obtained by needle biopsy and that liver tissue obtained by wedge section was desirable for study. These changes appear to be identical to those described by Sama et a1 (10) as noncirrhotic portal fibrosis of unknown cause. Obstruction of the portal vein has not been noted
in patients with Felty's syndrome and was specifically not present in 4 of the reviewed cases. Thus portal vein obstruction would not seem to contribute to the portal hypertension. The occurrence of esophageal varices is no doubt due to the portal hypertension seen in these cases and probably reflects the chronicity of the process. The mode of treatment in these patients needs to be evaluated further. Four of these patients had simple splenectomy; 1 died soon after surgery with an infection but none had recurrent hemorrhage during their followup period. One patient with splenectomy and a splenorenal shunt has also done well. In analyzing 28 operated cases of bleeding esophageal varices due to noncirrhotic portal fibrosis (none had rheumatoid arthritis), Sama et a1 noted that 3 of 25 cases treated with portal-systemic shunt procedures had recurrent hemorrhage from varices, whereas 1 of the 3 patients treated with simple splenectomy had recurrent hemorrhage (10). Simple splenectomy in the present case led to an immediate drop in portal pressure and apparent protection against variceal bleeding, even though the varices did not completely recede after 9 months. Reynolds has noted that esophageal varices often do not disappear even after portal-systemic shunt procedures (1 I). More intensive study of this subgroup of Felty's syndrome is obviously needed before firm conclusions can be made about the etiology of portal hypertension and the most beneficial form of treatment. However the
KLOFKORN ET AL Table 2. Portal System-Results
2
1
Patient
3
of Surgery
5
4
7
6
Varices Variceal hemorrhage Spleen size
Yes Yes
Yes No
Yes Yes
Yes No
Yes Yes
Yes No
Yes Yes
1140 g
1500 g
450 g
I248 g
570 g
650 g
Liver size
8-cm span
4 cm
5 cm below RCM NR
4 cm below LCM 4 cm below RCM Not examined
NR*
“Enlarged”
NR
Nodular
8 cm below RCM Smooth
Lobular fibrosis; Portal tract inportal tract infiltration with filtration with lymphocytes lymphocytes and plasma cells
“Some portal tract fibrosis without other features of cirrhosis”
Portal tract fibrosis and infiltration with lymphocpes
NR Patent Splenic pulp: 41 cm H,O
NR Patent Splenic pulp: 37 cm H,O
NR NR “Elevated”
NR NR NR
Diffuse fine nodulation, condensed reticulin trabeculae, round cell infiltration NR NR NR
Splenectomy, splenorenal shunt N o bleeding, liver function stable
N o surgery
Splenectomy
Splenectomy
Varices oversewn
No follow-up available
N o bleeding at N o bleeding, de- Died 3 days after 10 months after terioration in laporotomy with splenectomy liver function, massive variceal hemorrhage died 6 months after splenectomy with pontine hemorrhage
below RCM Finely nodular
Gross appearance Finely nodular of liver Liver biopsy Mild fatty Minimal portal metamorphosis tract fibrosis
Splenic artery Portal vein Portal pressure
Enlarged Patent Direct: 39 cm H,O
Treatment
Splenectomy
Results of treatment
Portal pressure Died with 18 cm H,O, n o septicemia 2 bleeding, liver weeks after function stable splenectomy
Enlarged Patent Splenic pulp?: 20 mm Hg 27 mm Hg Splenectomy
* Not reported.
t Two separate studies. presence of hemorrhage from esophageal varices, and perhaps the presence of uncomplicated portal hypertension, should be considered another possible indication for splenectomy in Felty’s syndrome.
ACKNOWLEDGMENT The authors are indebted to Mr. Robert J. Greaves, Medical Illustrator, and to the Medical Photography Laboratory of the Naval Regional Medical Center, San Diego, for the diagram and photographs.
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