SOLVING CLINICAL PROBLEMS IN BLOOD DISEASES
AJH Educational Material
A JH
A physician or group of physicians considers presentation and evolution of a real clinical case, reacting to clinical information and data (boldface type). This is followed by a discussion/commentary
Searching for the leak Daniel Shepshelovich,1,2* Talia Diker-Cohen,1,2,3 and Meir Lahav1,2,4
A 60-year-old woman was admitted for evaluation of a two day history of afebrile watery diarrhea, nausea, vomiting, and diffuse abdominal pain. She had not eaten outside her home, has not traveled recently and has not been exposed to animals. No one in her vicinity had similar symptoms. Although the differential diagnosis for abdominal pain, diarrhea, and vomiting is broad, I would first consider infectious gastroenteritis, the most common cause of acute diarrhea. A targeted medical history for recent travel, antibiotic treatment, similar symptoms in relatives or coworkers and eating out may offer diagnostic clues. Noninfectious causes of acute diarrhea in a 60-year-old patient include medications’ side effects, ischemic colitis, and diverticulitis. Conditions causing chronic diarrhea might be confused with acute diarrhea early in their course. The patient’s past medical history was significant for untreated stage II chronic lymphocytic leukemia (CLL) known for 3 years, with splenomegaly, stable lymphocytosis, and otherwise normal blood counts. She also had essential hypertension and hypertriglyceridemia. Her medications were ramipril, disothiazide, bezafibrate, and aspirin. Diarrhea in patients with CLL can have many etiologies. Acute diarrhea is commonly infectious and unrelated to CLL, with most pathogens being viruses (e.g., adenovirus, rotavirus, and Norwalk virus) or various bacteria (e.g., Escherichia coli, Clostridium difficile, Campylobacter jejuni, Salmonella, and Shigella spp.). Opportunistic pathogens (e.g., microsporidia and cryptosporidium) are more common after treatment with immunomodulating drugs (e.g., fludarabine). Noninfectious causes include chemotherapy-related diarrhea, which can be life threatening. CLL itself might rarely cause diarrhea through direct bowel involvement. On physical examination, the blood pressure was 90/55 mmHg, pulse 60 beats/min, temperature 35 C and respiratory rate 18. There was diffuse abdominal tenderness but no peritoneal irritation; the liver span was 12 cm in the midclavicular line; the spleen was palpated 4 cm below the rib line. Labs showed a white-cell count of 14,000 mm23 (68% lymphocytes), hematocrit level at 37.5%, and platelet count at 120 mm23. The serum sodium level was 133 mmol/l, potassium 4.3 mmol/l, urea 52 mg/dl, and creatinine 1.68 mg/dl (the patient’s baseline creatinine level was 0.87 mg/dl). Arterial blood gas results were normal.
The approach to a patient with acute diarrhea depends on its severity and the patient’s comorbidities. This patient’s hypotension and acute renal failure warrant further workup. Leukocytosis and thrombocytopenia could indicate severe infection, but could also be CLL-related. I would start with intravenous infusion of isotonic saline, order blood and stool cultures and proceed with hemodynamic and laboratory monitoring while rehydrating the patient. The patient received aggressive hydration therapy and was treated empirically with intravenous ciprofloxacin and metronidazole for a presumed intra-abdominal major infection. A computed tomography (CT) scan performed to rule out surgical conditions causing the profound abdominal tenderness showed no inflammatory focus. However, the scan demonstrated splenomegaly, a smallto-moderate amount of ascites and edema of the terminal ileum. Following hydration, the patients’ condition rapidly improved. The diarrhea and abdominal pain subsided within 24 hr, and the blood pressure and renal function normalized. Blood and stool cultures were negative and the antibiotic treatment was stopped. The patient was discharged in good condition. The findings of ascites and edema of the terminal ileum are unusual for simple gastroenteritis. The rapid response to fluid administration and antibiotics is also unexpected for a severe gastrointestinal infection. Addisonian crisis could present with hypotension, diarrhea, and ascites. CLL itself could cause ascites, terminal ileitis, and diarrhea through direct bowel involvement. This patient’s splenomegaly could suggest liver cirrhosis as a cause of ascites, although probably a manifestation of her CLL. Uncommon causes of diarrhea, ascites and terminal ileitis include yersinia and tuberculosis infections, Crohn’s disease, eosinophilic gastroenteritis, and systemic mastocytosis. Three days after recovery, the patient was readmitted for recurrence of afebrile diarrhea, nausea, vomiting, abdominal pain, and hypotension. Physical examination again showed diffuse abdominal tenderness with no peritoneal irritation, splenomegaly, and shifting dullness. Laboratory results demonstrated leukocytosis, lymphocytosis, and increased levels of urea and creatinine. Electrolytes were normal. Abdominal ultrasound revealed fatty liver, splenomegaly, and mild ascites. Blood and stool cultures were negative, as was a test for Clostridium difficile toxin. The patient was treated with saline and ciprofloxacin with rapid clinical recovery and resolution
1
Medicine A, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel; 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; 4Institute of Hematology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
Conflict of interest: Nothing to report D. S. and T. D. -C. have equally contributed to the work and writing of the manuscript *Correspondence to: Daniel Shepshelovich, Department of Medicine A, Rabin Medical Center, Beilinson Campus, Petah-Tikva, 49100 Israel. E-mail: [email protected] Received for publication: 15 April 2014; Accepted: 14 May 2014 Am. J. Hematol. 89:928–930, 2014. Published online: 21 May 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/ajh.23763 C 2014 Wiley Periodicals, Inc. V
928
American Journal of Hematology, Vol. 89, No. 9, September 2014
doi:10.1002/ajh.23763
SOLVING CLINICAL PROBLEMS IN BLOOD DISEASES
Figure 1. Course of C1 inhibitor concentration (mg%) related to rituximab administration over a 6-year period.
of renal failure. She was discharged feeling well, without pain or diarrhea. Recurrence of hypotension and acute renal failure after complete resolution of infectious gastroenteritis is uncommon. A different diagnosis should be pursued as the events recur and cause hemodynamic instability. I would order an adrenocorticotropic hormone stimulation test to rule out adrenal insufficiency and blood levels of tryptase to test for mastocytosis, tap the ascites for albumin level, complete blood count, culture and cytology, and consider a colonoscopy with biopsy of the terminal ileum. Two days after the second discharge, the patient was readmitted for similar symptoms. CT scan findings were consistent with persistence of ascites and edematous small bowel loops. Colonoscopy and gastroscopy were unremarkable as was upper gastrointestinal and small bowel series. Recurrent hypotension, ascites and edematous bowel loops could all be caused by episodes of increased vascular permeability. Severe infection could be the etiology of such findings, but not of recurrent events. Moreover, in this patient blood and stool cultures were repeatedly negative. Nephrotic syndrome and protein loosing enteropathy, common causes of edema, are not cyclical and do not cause acute exacerbations. Carcinoid syndrome can cause hypotension but is rarely the cause of severe edema and shock. Detailed history for agents and conditions potentially causing anaphylaxis should be obtained. Acquired angioedema (AAE) and systemic capillary leak syndrome (Clarkson syndrome), both rare entities with somewhat increased prevalence in patients with hematologic malignancies, should be considered. Laboratory evaluation for systemic mastocytosis and carcinoid syndrome were negative. Complement studies showed undetectable levels of C4 at
AJH Educational Material
A JH
A physician or group of physicians considers presentation and evolution of a real clinical case, reacting to clinical information and data (boldface type). This is followed by a discussion/commentary
Searching for the leak Daniel Shepshelovich,1,2* Talia Diker-Cohen,1,2,3 and Meir Lahav1,2,4
A 60-year-old woman was admitted for evaluation of a two day history of afebrile watery diarrhea, nausea, vomiting, and diffuse abdominal pain. She had not eaten outside her home, has not traveled recently and has not been exposed to animals. No one in her vicinity had similar symptoms. Although the differential diagnosis for abdominal pain, diarrhea, and vomiting is broad, I would first consider infectious gastroenteritis, the most common cause of acute diarrhea. A targeted medical history for recent travel, antibiotic treatment, similar symptoms in relatives or coworkers and eating out may offer diagnostic clues. Noninfectious causes of acute diarrhea in a 60-year-old patient include medications’ side effects, ischemic colitis, and diverticulitis. Conditions causing chronic diarrhea might be confused with acute diarrhea early in their course. The patient’s past medical history was significant for untreated stage II chronic lymphocytic leukemia (CLL) known for 3 years, with splenomegaly, stable lymphocytosis, and otherwise normal blood counts. She also had essential hypertension and hypertriglyceridemia. Her medications were ramipril, disothiazide, bezafibrate, and aspirin. Diarrhea in patients with CLL can have many etiologies. Acute diarrhea is commonly infectious and unrelated to CLL, with most pathogens being viruses (e.g., adenovirus, rotavirus, and Norwalk virus) or various bacteria (e.g., Escherichia coli, Clostridium difficile, Campylobacter jejuni, Salmonella, and Shigella spp.). Opportunistic pathogens (e.g., microsporidia and cryptosporidium) are more common after treatment with immunomodulating drugs (e.g., fludarabine). Noninfectious causes include chemotherapy-related diarrhea, which can be life threatening. CLL itself might rarely cause diarrhea through direct bowel involvement. On physical examination, the blood pressure was 90/55 mmHg, pulse 60 beats/min, temperature 35 C and respiratory rate 18. There was diffuse abdominal tenderness but no peritoneal irritation; the liver span was 12 cm in the midclavicular line; the spleen was palpated 4 cm below the rib line. Labs showed a white-cell count of 14,000 mm23 (68% lymphocytes), hematocrit level at 37.5%, and platelet count at 120 mm23. The serum sodium level was 133 mmol/l, potassium 4.3 mmol/l, urea 52 mg/dl, and creatinine 1.68 mg/dl (the patient’s baseline creatinine level was 0.87 mg/dl). Arterial blood gas results were normal.
The approach to a patient with acute diarrhea depends on its severity and the patient’s comorbidities. This patient’s hypotension and acute renal failure warrant further workup. Leukocytosis and thrombocytopenia could indicate severe infection, but could also be CLL-related. I would start with intravenous infusion of isotonic saline, order blood and stool cultures and proceed with hemodynamic and laboratory monitoring while rehydrating the patient. The patient received aggressive hydration therapy and was treated empirically with intravenous ciprofloxacin and metronidazole for a presumed intra-abdominal major infection. A computed tomography (CT) scan performed to rule out surgical conditions causing the profound abdominal tenderness showed no inflammatory focus. However, the scan demonstrated splenomegaly, a smallto-moderate amount of ascites and edema of the terminal ileum. Following hydration, the patients’ condition rapidly improved. The diarrhea and abdominal pain subsided within 24 hr, and the blood pressure and renal function normalized. Blood and stool cultures were negative and the antibiotic treatment was stopped. The patient was discharged in good condition. The findings of ascites and edema of the terminal ileum are unusual for simple gastroenteritis. The rapid response to fluid administration and antibiotics is also unexpected for a severe gastrointestinal infection. Addisonian crisis could present with hypotension, diarrhea, and ascites. CLL itself could cause ascites, terminal ileitis, and diarrhea through direct bowel involvement. This patient’s splenomegaly could suggest liver cirrhosis as a cause of ascites, although probably a manifestation of her CLL. Uncommon causes of diarrhea, ascites and terminal ileitis include yersinia and tuberculosis infections, Crohn’s disease, eosinophilic gastroenteritis, and systemic mastocytosis. Three days after recovery, the patient was readmitted for recurrence of afebrile diarrhea, nausea, vomiting, abdominal pain, and hypotension. Physical examination again showed diffuse abdominal tenderness with no peritoneal irritation, splenomegaly, and shifting dullness. Laboratory results demonstrated leukocytosis, lymphocytosis, and increased levels of urea and creatinine. Electrolytes were normal. Abdominal ultrasound revealed fatty liver, splenomegaly, and mild ascites. Blood and stool cultures were negative, as was a test for Clostridium difficile toxin. The patient was treated with saline and ciprofloxacin with rapid clinical recovery and resolution
1
Medicine A, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel; 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; 4Institute of Hematology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
Conflict of interest: Nothing to report D. S. and T. D. -C. have equally contributed to the work and writing of the manuscript *Correspondence to: Daniel Shepshelovich, Department of Medicine A, Rabin Medical Center, Beilinson Campus, Petah-Tikva, 49100 Israel. E-mail: [email protected] Received for publication: 15 April 2014; Accepted: 14 May 2014 Am. J. Hematol. 89:928–930, 2014. Published online: 21 May 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/ajh.23763 C 2014 Wiley Periodicals, Inc. V
928
American Journal of Hematology, Vol. 89, No. 9, September 2014
doi:10.1002/ajh.23763
SOLVING CLINICAL PROBLEMS IN BLOOD DISEASES
Figure 1. Course of C1 inhibitor concentration (mg%) related to rituximab administration over a 6-year period.
of renal failure. She was discharged feeling well, without pain or diarrhea. Recurrence of hypotension and acute renal failure after complete resolution of infectious gastroenteritis is uncommon. A different diagnosis should be pursued as the events recur and cause hemodynamic instability. I would order an adrenocorticotropic hormone stimulation test to rule out adrenal insufficiency and blood levels of tryptase to test for mastocytosis, tap the ascites for albumin level, complete blood count, culture and cytology, and consider a colonoscopy with biopsy of the terminal ileum. Two days after the second discharge, the patient was readmitted for similar symptoms. CT scan findings were consistent with persistence of ascites and edematous small bowel loops. Colonoscopy and gastroscopy were unremarkable as was upper gastrointestinal and small bowel series. Recurrent hypotension, ascites and edematous bowel loops could all be caused by episodes of increased vascular permeability. Severe infection could be the etiology of such findings, but not of recurrent events. Moreover, in this patient blood and stool cultures were repeatedly negative. Nephrotic syndrome and protein loosing enteropathy, common causes of edema, are not cyclical and do not cause acute exacerbations. Carcinoid syndrome can cause hypotension but is rarely the cause of severe edema and shock. Detailed history for agents and conditions potentially causing anaphylaxis should be obtained. Acquired angioedema (AAE) and systemic capillary leak syndrome (Clarkson syndrome), both rare entities with somewhat increased prevalence in patients with hematologic malignancies, should be considered. Laboratory evaluation for systemic mastocytosis and carcinoid syndrome were negative. Complement studies showed undetectable levels of C4 at
