CASE REPORTS
local constrictive occlusion may occur.5 The common arteriographic findings usually include symmetrical, smooth, tapered narrowing of major arteries such as the femoral or brachial. Although muscular arteries of the extremities are more susceptible, cases of renal, coronary, mesenteric and carotid involvement have been reported.6 The proximal vessels are usually free of atheromata, and this finding assists in making the diagnosis. Because of stasis and endothelial injury, thrombosis may be observed, although this is infrequent. Occasionally collaterals may be prominent initially, and regress as the spasm subsides. Why these collaterals in some people are less responsive to ergot toxicity is not known, but their function may favorably influence the prognosis. Most patients respond promptly to discontinuance of ergot administration. Systemic heparin and low molecular weight dextran may offer some protection from distal thrombosis, and may improve flow in the microvasculature in persons with severe ischemia.1 Adrenergic blockade is of little value because of the direct effect of ergot, and vasodilators have not been consistently useful, although in some cases benefit has been reported. Immediate and permanent cessation of ergot administration is the cornerstone of treatment and without establishing gangrene the prognosis is very good. If amputation is required, excellent healing of the stump can be anticipated after resolution of the vasospasm.
Summary Ergotamine tartrate, widely used in the treatment of migraine, may cause severe ischemia with chronic administration. The syndrome is more commonly seen in young women and pain and paresthesias are common manifestations. Arteriographic findings usually are diagnostic, and arteriography is recommended. Cessation of ergot administration is effective therapy, and intravenously given heparin and dextran may be useful adjuncts in patients with severe ischemia. REFERENCES 1. Henry LG, Blackwood JS, Conley JE, Bernhard VM: Ergotism. Arch Surg 110:929, 1975 2. Merhoff GC, Porter JM: Ergot intoxication-Historical review and description of unusual clinical manifestations. Ann Surg 180:773, 1974 3. Goodman L, Gillman A (Eds): The Pharmacological Basis of Therapeutics. New York, Macmillan Publishing Co, 1970. p 897 4. Bagley R, Cooper RD: Angiography in ergotism-Report of two cases and review of the literature. Am J Rcent Rad Ther Nucl Med 116:179, 1972 5. Kempczinski RF, Buckley CJ, Darling RC: Vascular insufficiency secondary to ergotism. Surgery 79:597, 1976 6. Richter AM, Bonkey VP: Carotid ergotism, a complication of migraine therapy. Radiology 106:339, 1970
248
SEPTEMBER 1977 * 127 * 3
Refer to: Koeffler HP, Cline MJ: Multiple myeloma presenting as ascites. West J Med 127: 248-250 Sep 1977
Multiple Myeloma Presenting as Ascites H. PHILLIP KOEFFLER, MD MARTIN J. CLINE, MD Los Angeles
ASCITES RAREI1Y DEVELOPS in patients with multiple myeloma.'-6 Even less frequent is ascites caused by peritoneal infiltration with myeloma cells.2-0 A surprisingly high percentage of those rare patients with myelomatous ascites have had an IgA paraprotein and no bony abnormalities.3,4 The triad of myelomatous ascites, an IgA paraprotein and lack of bone lesions may represent a distinct clinicopathologic entity.
Report of a Case In a 57-year-old white woman there was progressive abdominal swelling of one-month duration causing her moderate discomfort. She had been in good health before this time. She was admitted to hospital for investigation of the cause of the abdominal swelling. Physical examination revealed a grossly distended abdomen with an easily felt fluid wave. No lymphadenopathy, ecchymosis, bone tenderness or abnormality of retinal vessels was present. Laboratory results included a hematocrit of 20 percent and a leukocyte count of 4.2 X 109 per liter with a normal differential. Rouleau formation was not observed. The platelet count was 200 X 109 per liter, the blood urea nitrogen reading was 24 mg per dl; the albumin value was 2.6 grams per dl; the alkaline phosphatase and bilirubin levels were within normal limits. Analysis of urine showed four to five red blood cells per high power field, From the Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, School of Medicine. Submitted, revised, October 13, 1976. Reprint requests to: H. Phillip Koeffler, MD, Division of Hematology-Oncology. Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024.
CASE REPORTS
1.-Representative plasma cells present (Wright's stain).
Figure
the
in
ascitic fluid
eight
to nine
leukocytes
protein
2 grams of
high
per
power field and
per 24-hour urine collection.
yielded a yellow, slightly hemorspecific gravity was 1.028, total protein 2.5 grams per dl, bacteriological and fungal cultures were negative. Wright's stain of a Paracentesis
fluid. The
rhagic
centrifuged of
sheets
fluid
ascitic
of
specimen
showed
immature
plasma cells, some having (Figure 1).
nuclei with nucleoli
plasma cells in the ascitic fluid prompted further investigations. Bone marrow examination showed 20 percent immature plasma cells with The
large nucleoli and abnormal mitoses
multiple myeloma.
with seen
on
tative
a
roentgenographic
serum
1,1I00
(normal
were
bone survey. Quanti-
levels
(normal 120 ±70 the
IgA,
were:
3 8 0±-90 mg per
(normal 1,240±440
29 mg per dl
co-nsistent
abnormalities
immu'noglobulin
mg per dl
300 mg per dl
IgM,
No
dl); IgG,
mg per
dl);
mg per
dl).
showed
a electrophoresis the dl in of monoclonal peak gamma 1,010 mg per region. The urine protein electrophoresis had a 90 mg per dl monoclonal spike in the gamma region. The ascitic fluid did not have a monoclonal peak
Protein
on
on
serum
protein electrophoresis. The serum, urine and fluid showed an IgA-lambda paraprotein
ascitic on
immunoelectrophoresis.
Discussion The
multiple myeloma usually associated with
of
appearance is
in
ascites
rare.
When it
patient with develops, it is
a
with extensive liver infiltration
plasma cells, infectious peritonitis
lomatous
peritoneal
Approximately tiple myeloma
70 percent of
have
or
mye-
infiltration.'-
plasma
patients
cell
with mul-
infiltration
tissues outside the bone marrow.7' 8The liver is
of one
of the most frequent sites of extramedullary myeloma cell invasion. Thomas and his colleagues1 reported that liver infiltration with myeloma cells occurred in 40 percent of a series of 64 multiple myeloma patients. Ten percent of the patients in their series had extensive myelomatous liver infiltration and ascites. These patients did not have peritoneal plasma cell infiltrates, congestive heart failure or nephrosis. The authors felt that the ascites could best be explained by postsinusoidal portal hypertension. Peritoneal infiltration with myeloma cells has rarely been reported to occur in multiple myeloma. In a review of the literature to 1950, Hayes could document only three cases of peritoneal involvement with myeloma cells.7 Ascites developing from proven myeloma peritoneal infiltration is extremely infrequent.2-6 Durant and Barry described a patient with multiple myeloma and exudative ascites.9 The ascitic fluid contained plasma cells. However, peritoneal myeloma cell infiltrates were never proven by biopsy. Of the six patients, including the authors', established by biopsy or autopsy to have myelomatous peritoneal implants producing ascites, three had an IgA monoclonal spike.3'4 Of the remaining cases, one patient had an IgG paraprotein, another patient had only Bence Jones proteinuria and in the last case, the type of paraprotein was not reported.2'5'6 Two of the three patients with IgA paraprotein had no abnormalities on bone survey and the authors of the third report do not mention bone lesions.3'4 In a review of 869 cases of multiple myeloma seen at the Mayo Clinic, only 24 percent of the patients had an IgA serum paraprotein and 79 percent of the patients had bony abnormalities seen on roentgenograms of the
skeleton.'0 Because of the rarity of myelomatous ascites, it is difficult to know if the triad of myelomatous ascites, IgA paraprotein and absence of bone lesions is mere chance or represents a distinct clinical entity. It is noteworthy that in the lamina propria and base of the villi of the intestines there are abundant plasma cells which secrete predominantly IgA."1 In mice of the BALB/c strain, when injected intraperitoneally with Freund's adjuvant or mineral oil, ascites and peritoneal plasmacytomas that frequently secrete an IgA paraprotein develop.'2 Bone lesions do not develop in these mice. Patients with alpha heavy chain disease have an IgA heavy chain paraprotein. These patients' predominant clinicopathologic features cenTHE WESTERN JOURNAL OF MEDICINE
249
CASE REPORTS
ter in the abdomen and they have no destructive bone lesions.' It may be that cases with IgA myelomatous ascites represent a distinct clinical entity whose predominant clinical symptomatology is in the abdomen similar to alpha heavy chain disease.
Summary The case of a patient with ascites produced by peritoneal infiltration with myeloma cells is described and similar cases are reviewed. Of six patients (including the present one), in whom results of autopsy or biopsy showed there were myelomatous peritoneal implants producing ascites, at least three had an IgA paraprotein. Two of the three patients with the IgA paraprotein had no bony abnormalities on skeletal roentgenograms; the third case report mentions no bone lesions. The triad of myelomatous ascites, IgA paraprotein and absence of bone lesions on skeletal roentgenograms may represent a distinct clinicopathological syndrome.
REFERENCES 1. Thomas FB, Clausen KP, Greenberger NJ: Liver disease in multiple myeloma. Arch Intern Med 132:195-202, Aug 1973 2. Poth JL, George RP: Hemorrhagic ascites: An unusual complication of multiple myeloma. Calif Med 115:61-64, Sep 1971 3. Higby DJ, Ohnuma T: Plasmacytoma cell ascites. NY State J Med 75:1074-1076, Jun 1975 4. Bank H, Liberman SI: Sister Joseph's nodule and malignant ascites in multiple myeloma. N Engl J Med 284:676.677, Mar 1971 5. Line DH, Lewis RH: Gastric plasmacytoma. Gut 10:230-233, Mar 1969 6. Lucas RU, Schneider JR, Axelrod AR: Multiple myeloma with massive ascites-Report of a case. Harper Hosp Bull 26: 216-220, 1968 7. Hayes DW, Bennett WA, Heck FJ: Extramedullary lesions in multiple myeloma-Review of literature and pathologic studies. Arch Pathol 53:262-272, Mar 1952 8. Churg J, Gordon AJ: Multiple myeloma-Lesions of the extra-osseous hematopoietic system. Am J Clin Pathol 20:934-945, Oct 1950 9. Durant JR, Barry WE, Learner N: The changing face of myeloma. Lancet 1:119-121, Jan 1966 10. Kyle RA: Multiple myeloma-Review of 869 cases. Mayo Clin Proc 50:29-40, Jan 1975 11. Crabbe PA, Carbonara AO, Heremans JF: The normal human intestinal mucosa as a major source of plasma cells containing gamma-a-immunoglobulin. Lab Invest 14:235-248, May 1975 12. Potter M, Boyce CR: Induction of plasma-cell neoplasma in strain BALB/c mice with mineral oil and mineral oil adjuvants. Nature 193:1086-1087, May 1962 13. Seligmann M, Danon F, Hurez D, et al: Alpha-chain disease: A new immunoglobulin abnormality. Science 162:1396-1397, Dec 1968
Removing
a Honeybee Stinger The honeybee leaves the stinger in the recipient. The stinging apparatus is serrated, so that when it sticks in, it's stuck there. It's stuck like a fish hook. And the honeybee merely flies away, leaving part of the venom sac and part of the intestine
along with it, and this makes it rather hazardous, because frequently the person stung will try to get rid of this stinger, because it does sting. And this only adds to the insult by injecting more venom than if it had been left alone. And sometimes physicians or first-aid personnel attempt to get hold of the stinger and remove it, and in so doing they press more venom out of the sac and only add insult to injury. So that in removing the honeybee stinger, using a sharp knife or a fingernail just to flip it out is the ideal method. -RUSSELL 1. WiLLIAMS, MD, Denv er Extracted from Audio-Digest Family Practice, Vol. 24, No. 39, in the Audio-Digest Foundation's subscription series of taperecorded programs. For subscription information: 1577 East Chevy Chase Drive, Glendale, CA 91206.
250
SEPTEMBER 1977 * 127 * 3
local constrictive occlusion may occur.5 The common arteriographic findings usually include symmetrical, smooth, tapered narrowing of major arteries such as the femoral or brachial. Although muscular arteries of the extremities are more susceptible, cases of renal, coronary, mesenteric and carotid involvement have been reported.6 The proximal vessels are usually free of atheromata, and this finding assists in making the diagnosis. Because of stasis and endothelial injury, thrombosis may be observed, although this is infrequent. Occasionally collaterals may be prominent initially, and regress as the spasm subsides. Why these collaterals in some people are less responsive to ergot toxicity is not known, but their function may favorably influence the prognosis. Most patients respond promptly to discontinuance of ergot administration. Systemic heparin and low molecular weight dextran may offer some protection from distal thrombosis, and may improve flow in the microvasculature in persons with severe ischemia.1 Adrenergic blockade is of little value because of the direct effect of ergot, and vasodilators have not been consistently useful, although in some cases benefit has been reported. Immediate and permanent cessation of ergot administration is the cornerstone of treatment and without establishing gangrene the prognosis is very good. If amputation is required, excellent healing of the stump can be anticipated after resolution of the vasospasm.
Summary Ergotamine tartrate, widely used in the treatment of migraine, may cause severe ischemia with chronic administration. The syndrome is more commonly seen in young women and pain and paresthesias are common manifestations. Arteriographic findings usually are diagnostic, and arteriography is recommended. Cessation of ergot administration is effective therapy, and intravenously given heparin and dextran may be useful adjuncts in patients with severe ischemia. REFERENCES 1. Henry LG, Blackwood JS, Conley JE, Bernhard VM: Ergotism. Arch Surg 110:929, 1975 2. Merhoff GC, Porter JM: Ergot intoxication-Historical review and description of unusual clinical manifestations. Ann Surg 180:773, 1974 3. Goodman L, Gillman A (Eds): The Pharmacological Basis of Therapeutics. New York, Macmillan Publishing Co, 1970. p 897 4. Bagley R, Cooper RD: Angiography in ergotism-Report of two cases and review of the literature. Am J Rcent Rad Ther Nucl Med 116:179, 1972 5. Kempczinski RF, Buckley CJ, Darling RC: Vascular insufficiency secondary to ergotism. Surgery 79:597, 1976 6. Richter AM, Bonkey VP: Carotid ergotism, a complication of migraine therapy. Radiology 106:339, 1970
248
SEPTEMBER 1977 * 127 * 3
Refer to: Koeffler HP, Cline MJ: Multiple myeloma presenting as ascites. West J Med 127: 248-250 Sep 1977
Multiple Myeloma Presenting as Ascites H. PHILLIP KOEFFLER, MD MARTIN J. CLINE, MD Los Angeles
ASCITES RAREI1Y DEVELOPS in patients with multiple myeloma.'-6 Even less frequent is ascites caused by peritoneal infiltration with myeloma cells.2-0 A surprisingly high percentage of those rare patients with myelomatous ascites have had an IgA paraprotein and no bony abnormalities.3,4 The triad of myelomatous ascites, an IgA paraprotein and lack of bone lesions may represent a distinct clinicopathologic entity.
Report of a Case In a 57-year-old white woman there was progressive abdominal swelling of one-month duration causing her moderate discomfort. She had been in good health before this time. She was admitted to hospital for investigation of the cause of the abdominal swelling. Physical examination revealed a grossly distended abdomen with an easily felt fluid wave. No lymphadenopathy, ecchymosis, bone tenderness or abnormality of retinal vessels was present. Laboratory results included a hematocrit of 20 percent and a leukocyte count of 4.2 X 109 per liter with a normal differential. Rouleau formation was not observed. The platelet count was 200 X 109 per liter, the blood urea nitrogen reading was 24 mg per dl; the albumin value was 2.6 grams per dl; the alkaline phosphatase and bilirubin levels were within normal limits. Analysis of urine showed four to five red blood cells per high power field, From the Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, School of Medicine. Submitted, revised, October 13, 1976. Reprint requests to: H. Phillip Koeffler, MD, Division of Hematology-Oncology. Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024.
CASE REPORTS
1.-Representative plasma cells present (Wright's stain).
Figure
the
in
ascitic fluid
eight
to nine
leukocytes
protein
2 grams of
high
per
power field and
per 24-hour urine collection.
yielded a yellow, slightly hemorspecific gravity was 1.028, total protein 2.5 grams per dl, bacteriological and fungal cultures were negative. Wright's stain of a Paracentesis
fluid. The
rhagic
centrifuged of
sheets
fluid
ascitic
of
specimen
showed
immature
plasma cells, some having (Figure 1).
nuclei with nucleoli
plasma cells in the ascitic fluid prompted further investigations. Bone marrow examination showed 20 percent immature plasma cells with The
large nucleoli and abnormal mitoses
multiple myeloma.
with seen
on
tative
a
roentgenographic
serum
1,1I00
(normal
were
bone survey. Quanti-
levels
(normal 120 ±70 the
IgA,
were:
3 8 0±-90 mg per
(normal 1,240±440
29 mg per dl
co-nsistent
abnormalities
immu'noglobulin
mg per dl
300 mg per dl
IgM,
No
dl); IgG,
mg per
dl);
mg per
dl).
showed
a electrophoresis the dl in of monoclonal peak gamma 1,010 mg per region. The urine protein electrophoresis had a 90 mg per dl monoclonal spike in the gamma region. The ascitic fluid did not have a monoclonal peak
Protein
on
on
serum
protein electrophoresis. The serum, urine and fluid showed an IgA-lambda paraprotein
ascitic on
immunoelectrophoresis.
Discussion The
multiple myeloma usually associated with
of
appearance is
in
ascites
rare.
When it
patient with develops, it is
a
with extensive liver infiltration
plasma cells, infectious peritonitis
lomatous
peritoneal
Approximately tiple myeloma
70 percent of
have
or
mye-
infiltration.'-
plasma
patients
cell
with mul-
infiltration
tissues outside the bone marrow.7' 8The liver is
of one
of the most frequent sites of extramedullary myeloma cell invasion. Thomas and his colleagues1 reported that liver infiltration with myeloma cells occurred in 40 percent of a series of 64 multiple myeloma patients. Ten percent of the patients in their series had extensive myelomatous liver infiltration and ascites. These patients did not have peritoneal plasma cell infiltrates, congestive heart failure or nephrosis. The authors felt that the ascites could best be explained by postsinusoidal portal hypertension. Peritoneal infiltration with myeloma cells has rarely been reported to occur in multiple myeloma. In a review of the literature to 1950, Hayes could document only three cases of peritoneal involvement with myeloma cells.7 Ascites developing from proven myeloma peritoneal infiltration is extremely infrequent.2-6 Durant and Barry described a patient with multiple myeloma and exudative ascites.9 The ascitic fluid contained plasma cells. However, peritoneal myeloma cell infiltrates were never proven by biopsy. Of the six patients, including the authors', established by biopsy or autopsy to have myelomatous peritoneal implants producing ascites, three had an IgA monoclonal spike.3'4 Of the remaining cases, one patient had an IgG paraprotein, another patient had only Bence Jones proteinuria and in the last case, the type of paraprotein was not reported.2'5'6 Two of the three patients with IgA paraprotein had no abnormalities on bone survey and the authors of the third report do not mention bone lesions.3'4 In a review of 869 cases of multiple myeloma seen at the Mayo Clinic, only 24 percent of the patients had an IgA serum paraprotein and 79 percent of the patients had bony abnormalities seen on roentgenograms of the
skeleton.'0 Because of the rarity of myelomatous ascites, it is difficult to know if the triad of myelomatous ascites, IgA paraprotein and absence of bone lesions is mere chance or represents a distinct clinical entity. It is noteworthy that in the lamina propria and base of the villi of the intestines there are abundant plasma cells which secrete predominantly IgA."1 In mice of the BALB/c strain, when injected intraperitoneally with Freund's adjuvant or mineral oil, ascites and peritoneal plasmacytomas that frequently secrete an IgA paraprotein develop.'2 Bone lesions do not develop in these mice. Patients with alpha heavy chain disease have an IgA heavy chain paraprotein. These patients' predominant clinicopathologic features cenTHE WESTERN JOURNAL OF MEDICINE
249
CASE REPORTS
ter in the abdomen and they have no destructive bone lesions.' It may be that cases with IgA myelomatous ascites represent a distinct clinical entity whose predominant clinical symptomatology is in the abdomen similar to alpha heavy chain disease.
Summary The case of a patient with ascites produced by peritoneal infiltration with myeloma cells is described and similar cases are reviewed. Of six patients (including the present one), in whom results of autopsy or biopsy showed there were myelomatous peritoneal implants producing ascites, at least three had an IgA paraprotein. Two of the three patients with the IgA paraprotein had no bony abnormalities on skeletal roentgenograms; the third case report mentions no bone lesions. The triad of myelomatous ascites, IgA paraprotein and absence of bone lesions on skeletal roentgenograms may represent a distinct clinicopathological syndrome.
REFERENCES 1. Thomas FB, Clausen KP, Greenberger NJ: Liver disease in multiple myeloma. Arch Intern Med 132:195-202, Aug 1973 2. Poth JL, George RP: Hemorrhagic ascites: An unusual complication of multiple myeloma. Calif Med 115:61-64, Sep 1971 3. Higby DJ, Ohnuma T: Plasmacytoma cell ascites. NY State J Med 75:1074-1076, Jun 1975 4. Bank H, Liberman SI: Sister Joseph's nodule and malignant ascites in multiple myeloma. N Engl J Med 284:676.677, Mar 1971 5. Line DH, Lewis RH: Gastric plasmacytoma. Gut 10:230-233, Mar 1969 6. Lucas RU, Schneider JR, Axelrod AR: Multiple myeloma with massive ascites-Report of a case. Harper Hosp Bull 26: 216-220, 1968 7. Hayes DW, Bennett WA, Heck FJ: Extramedullary lesions in multiple myeloma-Review of literature and pathologic studies. Arch Pathol 53:262-272, Mar 1952 8. Churg J, Gordon AJ: Multiple myeloma-Lesions of the extra-osseous hematopoietic system. Am J Clin Pathol 20:934-945, Oct 1950 9. Durant JR, Barry WE, Learner N: The changing face of myeloma. Lancet 1:119-121, Jan 1966 10. Kyle RA: Multiple myeloma-Review of 869 cases. Mayo Clin Proc 50:29-40, Jan 1975 11. Crabbe PA, Carbonara AO, Heremans JF: The normal human intestinal mucosa as a major source of plasma cells containing gamma-a-immunoglobulin. Lab Invest 14:235-248, May 1975 12. Potter M, Boyce CR: Induction of plasma-cell neoplasma in strain BALB/c mice with mineral oil and mineral oil adjuvants. Nature 193:1086-1087, May 1962 13. Seligmann M, Danon F, Hurez D, et al: Alpha-chain disease: A new immunoglobulin abnormality. Science 162:1396-1397, Dec 1968
Removing
a Honeybee Stinger The honeybee leaves the stinger in the recipient. The stinging apparatus is serrated, so that when it sticks in, it's stuck there. It's stuck like a fish hook. And the honeybee merely flies away, leaving part of the venom sac and part of the intestine
along with it, and this makes it rather hazardous, because frequently the person stung will try to get rid of this stinger, because it does sting. And this only adds to the insult by injecting more venom than if it had been left alone. And sometimes physicians or first-aid personnel attempt to get hold of the stinger and remove it, and in so doing they press more venom out of the sac and only add insult to injury. So that in removing the honeybee stinger, using a sharp knife or a fingernail just to flip it out is the ideal method. -RUSSELL 1. WiLLIAMS, MD, Denv er Extracted from Audio-Digest Family Practice, Vol. 24, No. 39, in the Audio-Digest Foundation's subscription series of taperecorded programs. For subscription information: 1577 East Chevy Chase Drive, Glendale, CA 91206.
250
SEPTEMBER 1977 * 127 * 3
