|
|
|
Case Report- A 52-Year-old with Dyspnea, Exertional Chest Pain and Bilateral Lower Extremity Edema |
CONSTANTINOS TZIROGIANNIS, MD
HISTORY OF PRESENT ILLNESS
A 52 year-old white male presented to the emergency department with progressively worsening bilateral lower extremity edema, dyspnea and chest pain. The patient started having chest pain and dyspnea on exertion one month prior to presentation. The pain was described as pressing, grade 6-7/10 in severity and without radiation. The patient also reported fevers with chills, unintentional weight loss, night sweats and generalized arthalgias and myalgias over the past month. The patient denied any nausea, vomiting, hematemesis, melena, recent changes in his bowel habits, rashes, easy bruisability, epistaxis, gingival hemorrhage or recent travel.
His past medical history was significant for rheumatoid arthritis diagnosed in 2000 and treated with non-steroidal anti-inflammatory drugs with adequate symptomatic control, a motor vehicle accident with multiple fractures in 1979 and hemorrhoids. His only home medications were non-steroidal anti-inflammatory medications. Social history was significant for smoking and alcohol, which he quit 18 years ago. He denied intravenous drug use but admitted to multiple high risk sexual contacts in the past. His family history was significant for coronary artery disease in his mother.
Physical Examination
The vital signs on admission included a temperature of 98.7 degrees Fahrenheit, blood pressure of 119/63 mm Hg, respiratory rate of 24 breaths per minute and heart rate of 116 bpm. The patient appeared pale and emaciated and in no acute distress. His skin had good turgor, without rashes, petecchiae or ecchymoses. The conjunctivae were pale and sclerae was anicteric. His neck was supple with multiple enlarged lymph nodes, the largest of which was great than 4 cm. Axillary palpation was also significant for multiple enlarged nodes with the largest node greater than 6 cm. He also had inguinal lymphadenopathy, with a 3 cm lymph node on the right. His lung exam was clear to auscultation bilaterally. Heart sounds were regular, with a grade III systolic ejection murmur best heard at the apex. The abdominal exam was remarkable for an enlarged liver palpated 4 cm below the costal margin and a markedly enlarged spleen at 15 cm below the left costal margin. The extremities showed bilateral 3+ edema below the knees.
DIFFERENTIAL DIAGNOSIS
Myeloproliferative disorders
Lymphoproliferative disorders
Leukemia
DATA
Table 1: Admission Laboratory Data.*
White blood cell count |
832,500/µL (H) |
Lymphocytes % |
99
(H) |
Segmented neutrophils % |
1
(L) |
Hematocrit |
10 % (L) |
Hemoglobin |
3.5 g/dl (L) |
Platelets |
56000/µL
(L) |
Total Bilirubin |
2 mg/dl
(H) |
Lactic dehydrogenase |
238 U/L |
*Note: (H) indicates high. (L) indicates low.
A peripheral smear showed red blood cells with mild anisocytosis, and a significantly elevated leukocyte count with the majority (estimated 60%) as mature appearing small lymphocytes. The remainder of the leukocyte population was intermediate to large lymphocytes and some contained prominent nucleoli. Granulocytes were rarely seen. Indirect and direct Coomb’s tests were negative. Flow cytometry of the peripheral blood revealed 98.5% CD19(+) (B cells), 100% CD5(+),96.7% CD 20(+), 99.5% CD 23 (+), 98% CD43(+), 98.9% IgD(+) and 95.5% Skappa (+).
Chest X-Ray showed cardiomegaly and a small right sided pleural effusion. An EKG showed ST segment depression in leads V4 and V5.
HOSPITAL COURSE
The patient was diagnosed with chronic lymphocytic leukemia (CLL), RAI’s stage IV, with high output cardiac failure due to severe secondary anemia. The diagnosis was made initially from peripheral blood smear and confirmed later by flow cytometry of peripheral blood.
He was transfused slowly with a total of five units of blood along with diuretic administration due to concern for exacerbation of his cardiac failure and induction of leukostasis from the rapid increase of his hematocrit and blood viscosity. Chemotherapy with a low dose alkylating agent was initiated with the objective of gradual control of the leukemia. Tumor lysis syndrome was also considered and the patient received allopurinol with continuous monitoring of his uric acid, phosphate and potassium levels. Aggressive hydration for tumor lysis syndrome was withheld due to the increased risk for a CHF exacerbation. The patient was discharged home on a low dose of cyclophosphamide and allopurinol.
At the time of discharge, the white blood cell count was trending down, with a significant reduction of lymphadenopathy and splenomegaly (12.5 cm below the costal margin).
DISCUSSION
CLL represents a clonal expansion of neoplastic lymphocytes (functionally incompetent) that possess the phenotype of mature activated B lymphocytes. The disorder is classified as a chronic lymphoproliferative disorder and according to the WHO classification, is considered identical (two different stages of the same disease) to mature peripheral B-cell small lymphocytic lymphoma.1
CLL has been traditionally considered an indolent disease with a prolonged clinical course and with the cause of death often being unrelated to the disorder. In the last decade this concept has significantly changed, as it has become evident that there is a wide spectrum of clinical manifestations and prognostic stratifications among patients with CLL. The indolent form of the disease is only seen in 30% of patients.2
The initial presenting findings of the disease encompass lymphadenopathy (87%), splenomegaly (54%), hepatomegaly (14%), white blood cell counts above 100,000/µL (30%), hemoglobin below 11g/dl (31%) and platelet counts below 100,000/µL (16%). The majority of patients with CLL consult their physician because of painless lymphadenopathy most often in the cervical area that fluctuates with time but never disappears.3 Occasionally, CLL may be clinically evident as an acquired immunodeficiency disorder or by autoimmune manifestations such as hemolytic anemia and thrombocytopenia, or less often as pure red cell aplasia or excessive local reaction to insect bites. In general, the clinical presentation varies greatly, with one end of the spectrum being the asymptomatic patients who are diagnosed due to accidentally found absolute lymphocytosis (25%) and the other end (5-10%) being patients who present with type B symptoms such as unintentional weight loss, fever above 100.5 F, night sweats and extreme fatigue.
Minimal diagnostic criteria for diagnosis of CLL are:
- Absolute lymphocyte count in the peripheral blood greater than 10,000/ µL with a preponderance of mature-appearing small lymphocytes.
- A normocellular or hypercellular bone marrow with lymphocytes accounting for greater than 30% of all nucleated cells.
- Lymphocyte phenotyping is required in patients with lymphocyte counts between 5,000 and 10,000/µL.
In a variable percentage of patients, and usually as a terminal event, CLL transforms to another lymphoproliferative disorder: prolymphocytic leukemia (10%), aggressive or highly aggressive lymphoma (3%), Hodgkin's disease (0.5%) and multiple myeloma (0.1%).
The clinical heterogeneity of CLL seems to reflect and be the result of diversity at the molecular level. Recognizing this heterogeneity, Rai and colleagues and Binet and colleagues have proposed staging systems for assessing the extensiveness of the disease and guiding treatment.4,5 These staging systems remain the cornerstone for initial staging and decisions guiding treatment, but fail to predict prognosis or course of disease at the early stages. The major clinical use of the above staging systems is to help clinicians decide when patients should be started on therapy. Accurate stratification of high and low risk groups of patients as well as accurate prognosis can be better achieved with systems of classification based on cellular and molecular phenotyping which are not currently routinely available.6 Watchful waiting had been the major clinical mode for many years but experts consider that this is going to change upon introduction of molecular prognostic features since half of the patients upon initial diagnosis are in the poor prognosis group and must expeditiously be started on therapy. One large scale clinical trial is currently in progress exploring this direction.
The historic backbone of chemotherapy for CLL was alkylating agents with or without steroids. This treatment was used until symptoms resolved or clinically evident lymphadenopathy or splenomegaly were controlled. Antimetabolites have not drawn great interest for the treatment of CLL due to the concept that only a small percentage of cells are in the S phase of the cell cycle. Recently, however, the introduction of purine analogues for the treatment of CLL has been accompanied by higher complete remission rates and their use has drawn clinical interest.
REFERENCES
- Harris NL., Jaffe ES., Diebold J., et all. World Health organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997, Journal of Clinical Oncology 1999, 17:3835.
- Cheson BD., Bennett JM., Rai KR., et al. Guidelines for clinical protocols for chronic lymphocytic leukemia. Recommendations of the NCI-Sponsored Working Group American Journal of Hematology 1988, 25:152
- Keating MJ., O’Brien S., Lerner S et al. Long term follow-up of patients with chronic lymphocytic leukemia receiving fludarabine regimens as initial therapy. Blood 1998, 92:1165.
- Rai KA., Sawitski A., Cronkite EP., Chanana AD., Levy RN., Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood 1975, 46:219-234
- Binet JL., Auquier A., Dighiero G., et al. A new prognostic classification of chronic lymphocytic leukemia derived from multivariate survival analysis. Cancer 1981, 48:198-206.
- Rassenti LZ., Huynh L., Toy TL., et al. ZAP-70 compared with immunoglobulin heavy chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. New England Journal of Medicine 2004, 351: 893-901.
|
|
|
