Recurrent Abdominal Pain and Bloody Stools

The n e w e ng l a n d j o u r na l of m e dic i n e
Case Records of the Massachusetts General Hospital
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Eric S. Rosenberg, M.D., Editor
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Case 8-2020: An 89-Year-Old Man with

Recurrent Abdominal Pain and Bloody Stools
Hacho B. Bohossian, M.D., Emily W. Lopes, M.D., Lauren A. Roller, M.D.,
Ashwin N. Ananthakrishnan, M.D., M.P.H., and Lawrence R. Zukerberg, M.D.
Pr e sen tat ion of C a se
From the Department of Medicine, New Dr. Emily W. Lopes: An 89-year-old man was evaluated at this hospital because of
ton–Wellesley Hospital, Newton (H.B.B.), recurrent bloody stools.
and the Department of Medicine, Tufts
University School of Medicine (H.B.B.), Two years before the current evaluation, the patient underwent repair of a right
the Departments of Medicine (E.W.L., inguinal hernia. After he recovered from that procedure, he had intermittent pain
A.N.A.), Radiology (L.A.R.), and Pathol in the right lower quadrant. Four months before the current evaluation, he was
ogy (L.R.Z.), Massachusetts General Hos
pital, and the Departments of Medicine admitted to this hospital for diffuse abdominal pain followed by presyncope dur-
(E.W.L., A.N.A.), Radiology (L.A.R.), and ing an attempt to defecate. Examination was notable for bilateral lower abdominal
Pathology (L.R.Z.), Harvard Medical tenderness and a crescendo–decrescendo systolic murmur (grade 2/6) at the left
School, Boston — all in Massachusetts.
sternal border. Laboratory test results are shown in Table 1.
N Engl J Med 2020;382:1042-52. Dr. Lauren A. Roller: Computed tomography (CT) of the abdomen and pelvis
DOI: 10.1056/NEJMcpc1913476
Copyright © 2020 Massachusetts Medical Society.
(Fig. 1A and 1B), performed after the administration of oral but not intravenous
contrast material, showed diverticulosis of the descending and sigmoid colon, with
focal areas of hyperemia and wall thickening in the distal descending colon. There
were atherosclerotic changes in the aorta and aortic branches, with a 36-mm infra-
renal aortic aneurysm. Small radiopaque stones were present in the gallbladder
and common bile duct.
Dr. Lopes: Several bowel movements with loose, nonbloody stools occurred, with
a decrease in abdominal pain. Empirical oral ciprofloxacin and metronidazole
were prescribed, and the patient was discharged on the third hospital day.
Two months later, the patient was readmitted to this hospital with a 3-week
history of progressively bloody stools and crampy, diffuse abdominal pain, which
had awakened him from sleep. The pain was worst before bowel movements,
which occurred approximately five times per day. Increasing amounts of red blood
were present in the stools. The patient reported no fever, anorexia, nausea, or
vomiting. Examination revealed abdominal tenderness, primarily in the lower
quadrants, and the presence of soft, red-brown, formed stool in the rectal vault
that was guaiac-positive. Laboratory test results are shown in Table 1. Two units
1042 n engl j med 382;11 nejm.org March 12, 2020
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Case Records of the Massachuset ts Gener al Hospital
Table 1. Laboratory Data.*
On First On Second On Third Day 9, Third On Current

Reference Range, Admission, Admission, Admission, Admission, Admission,
Variable Adults† This Hospital This Hospital This Hospital This Hospital This Hospital
Hemoglobin (g/dl) 13.5–17.5 11.7 8.8 11.3 9.8 9.4
Hematocrit (%) 41.0–53.0 37.9 27.7 36.4 30.9 29.4
White-cell count (per μl) 4500–11,000 10,140 5590 8030 9220 9670
Differential count (%)
Neutrophils 40–70 72.8 52.3 78.2 65.5 72.6
Lymphocytes 22–44 17.9 27.5 17.4 21.9 15.0
Monocytes 4–11 4.4 10.4 2.6 2.5 2.7
Eosinophils 0–8 4.1 8.9 0.9 1.7 0.9
Basophils 0–3 0.6 0.7 0 0 0
Bands 8.4 8.8
Platelet count (per μl) 150,000–400,000 152,000 102,000 129,000 85,000 103,000
Urea nitrogen (mg/dl) 8–25 35 27 31 39 36
Creatinine (mg/dl) 0.60–1.50 1.56 1.32 1.79 1.81 1.32
Albumin (g/dl) 3.3–5.0 3.8 3.6 3.5 2.3
Cytomegalovirus DNA (IU/ml) 137–9,100,000 421
C-reactive protein (mg/liter) <8 73.2 263.4
Erythrocyte sedimentation rate 0–13 36 117
(mm/hr)
IgG 614–1295 1183 1092
IgA 69–309 627 565
IgM 53–334 19 12
Serum protein electrophoresis No M component No M com No M com
ponent ponent
Kappa free light chain (mg/liter) 3.3–19.4 134.9
Lambda free light chain (mg/liter) 5.7–26.3 72.5
* To convert the values for urea nitrogen to millimoles per liter, multiply by 0.357. To convert the values for creatinine to micromoles per liter,
multiply by 88.4.
† Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at
Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They
may therefore not be appropriate for all patients.
of packed red cells were transfused. Aspirin was second hospital day, nucleic-acid testing of stool
discontinued, and a stool specimen was submit- was positive for Clostridioides difficile (formerly
ted for microbiologic evaluation. Clostridium difficile) toxin; ciprofloxacin was dis-
Dr. Roller: CT of the abdomen and pelvis continued. Three days later, abdominal discom-
(Fig. 1C), performed after the administration of fort persisted, and there were four or five bowel
intravenous and oral contrast material, showed a movements per day with blood and intermittent
long segment of circumferential wall thickening mucus in the stools. Oral vancomycin therapy
in the rectum and sigmoid colon and diverticu- was started, and metronidazole was discontin-
losis of the distal descending colon, without di- ued. During the next 3 days, the frequency of
verticulitis. bowel movements decreased to two per day, and
Dr. Lopes: Empirical treatment with oral cipro- the patient was discharged to complete 2 weeks
floxacin and metronidazole was started. On the of oral vancomycin therapy.
n engl j med 382;11 nejm.org March 12, 2020 1043

A Figure 1. CT Scans of the Abdomen and Pelvis

from the First and Second Admissions.
Coronal images obtained 4 months before the current
evaluation (first admission) (Panels A and B), after the
administration of oral but not intravenous contrast
material, show segmental wall thickening and mesen
teric inflammatory changes involving a short segment
of the distal descending colon, which contains multiple
diverticula (arrows). An axial image obtained 2 months
before the current evaluation (second admission)
(Panel C), after the administration of intravenous and
oral contrast material, shows segmental wall thickening,
mucosal enhancement and edema, and mesenteric
vascular engorgement involving the sigmoid colon and
rectum, without associated diverticula (arrow). The wall
thickening of the distal descending colon that was seen
during the first admission has resolved (arrowhead).
Two weeks after discharge, the frequency of

bowel movements increased to four to six per
day, with increasingly bloody stools but without
B abdominal pain. The dose of vancomycin was
increased. During the next week, the frequency
of bowel movements with bloody stools in-
creased to eight per day, with intermittent incon-
tinence of stool. The patient was admitted for
the third time to this hospital. On examination,
there was mild bilateral lower abdominal tender-
ness. The stool was guaiac-positive, and testing
for C. difficile toxin was negative; other laboratory
test results are shown in Table 1. Cultures of the
stool showed normal enteric flora and no patho-
genic bacteria.
On the fifth day, flexible sigmoidoscopy
(Fig. 2A and 2B) revealed diffusely hemorrhagic,
erythematous, congested, eroded, friable mucosa
in the sigmoid colon, with spontaneous bleeding
and pseudopolyps. Biopsy specimens were ob-
tained.
Dr. Lawrence R. Zukerberg: The next day, patho-
C logical analysis of the biopsy specimens revealed
evidence of markedly active chronic colitis, in-
cluding surface erosion, neutrophilic cryptitis,
crypt loss, and replacement of the lamina pro-
pria with a dense lymphoplasmacytic infiltrate
(Fig. 2C). Scattered cytomegalovirus (CMV) inclu-
sion bodies were detected on immunostaining
(Fig. 2D).
Dr. Lopes: Ganciclovir therapy was started, and
laboratory test results are shown in Table 1. Over
the next 4 days, there was no decrease in the
number of daily bowel movements, but the num-
ber of bloody stools decreased. Intermittent

A B
C D
Figure 2. Endoscopic Images and Biopsy Specimens from the Third Admission.
Images obtained during flexible sigmoidoscopy (Panels A and B) show diffusely erythematous, congested, eroded
(Panel A, arrow), friable mucosa in the sigmoid colon, with spontaneous bleeding (Panel B, arrow). Hematoxylin
and eosin staining of the biopsy specimens (Panel C) shows evidence of active chronic colitis, including replace
ment of the lamina propria with lymphocytes and plasma cells (single arrow) and surface erosion (double arrow).
Immunostaining (Panel D) shows cytomegalovirus inclusion bodies (in brown; arrows), a finding indicative of cyto
megalovirus infection.
anorexia and crampy lower abdominal pain oc- and genitourinary, cardiopulmonary, musculo-
curred. Ganciclovir was switched to valganci- skeletal, and dermatologic symptoms. There were
clovir. Over the next 6 days, the frequency of no specific sick contacts at the rehabilitation
bowel movements decreased to two to five per facility or residents with reported gastrointesti-
day, with a modest decrease in anorexia and nal illnesses.
abdominal pain. The patient was discharged to The patient’s medical history was notable for
a rehabilitation facility. coronary artery disease, moderate aortic steno-
Two weeks later, the patient had persistently sis, hypertension, left ventricular hypertrophy,
loose, yellow, foul-smelling stools. One week chronic renal insufficiency, glaucoma, and a
later, bloody stools recurred, and after a marked thyroid nodule; he had undergone aortocoronary-
increase in bloody stools over the following bypass grafting. Outpatient medications includ-
week, the patient was readmitted to this hospi- ed valganciclovir, simvastatin, cholecalciferol,
tal. He reported reduced appetite, an uninten- mirtazapine, a multivitamin, and latanoprost
tional loss of 3 kg during the past month, ten- eyedrops, as well as loperamide and diphenoxy-
derness on the left side of the abdomen, and late with atropine as needed. There were no ad-
diffuse weakness. A review of systems was verse reactions to medications.
negative for fever, other bleeding and bruising, The patient had retired from military service.

A B
C D
E F
Figure 3. CT Scan, Endoscopic Images, and Biopsy Specimens from the Current Admission.
Axial and coronal CT images (Panels A and B, respectively), obtained after the administration of intravenous and
oral contrast material, show contiguous wall thickening and mucosal enhancement and edema (arrows) involving
the entire colon; the rectum was also involved. Also shown is mural thrombus in an abdominal aortic aneurysm
(Panel A, arrowhead). Images obtained during flexible sigmoidoscopy (Panels C and D) show diffuse severe colonic
inflammation, erythema, edema, friability, and deep ulcerations (Panel C, arrow) in the rectum and sigmoid colon.
Hematoxylin and eosin staining of the biopsy specimens (Panels E and F) shows severely active chronic colitis char
acterized by replacement of the lamina propria with lymphocytes and plasma cells (Panel E), as well as a cleftshaped
embolus in a small vessel (Panel F, arrow).

He had no recent history of travel. He had last Dr. Zukerberg: Pathological examination of bi-
used tobacco three decades earlier, and he did opsy specimens of the rectum and sigmoid colon
not drink alcohol or use illicit substances. His (Fig. 3E and 3F) revealed evidence of severely
mother had had coronary artery disease and his active chronic colitis, including surface ulcer-
father had had a stroke; there was no family his- ation, replacement of the lamina propria with a
tory of infectious or autoimmune disease. dense lymphoplasmacytic infiltrate, and rare
The temperature was 36.1°C, the heart rate cholesterol emboli in small vessels. Immunohis-
89 beats per minute, the blood pressure 117/58 tochemical stains for CMV, herpes simplex virus
mm Hg, and the oxygen saturation 98% while types 1 and 2, and adenovirus were negative, as
the patient was breathing ambient air. He was a was a shell-vial culture for CMV.
frail-appearing elderly man with dry mucous Dr. Lopes: A diagnosis was made.
membranes and impaired dentition but no oro-
pharyngeal lesions. Cardiac auscultation revealed Differ en t i a l Di agnosis
a crescendo–decrescendo murmur (grade 2/6) at
the left sternal border. An abdominal examina- Dr. Hacho B. Bohossian: This 89-year-old man with
tion revealed tenderness on palpation of the right coronary artery disease presented with a several-
lower quadrant, without distention, rebound month history of bloody diarrhea and abdominal
guarding, or organomegaly. A rectal examina- pain. The bloody stools, abdominal pain, weight
tion revealed only a few small external hemor- loss, and rising erythrocyte sedimentation rate
rhoids, no palpable fissures or masses, slightly and C-reactive protein level suggest that the pa-
reduced rectal tone, and guaiac-positive, light- tient had chronic inflammatory diarrhea. The
red, loose stool with mucus. Peripheral pulses differential diagnosis includes infection, cancer,
were intact, and there were no rashes. The re- vascular causes, and noninfectious inflamma-
mainder of the examination was normal. tory causes.
Blood levels of electrolytes, lactate, bilirubin,
amylase, lipase, and troponin T and the results Infection
of liver-function tests were normal; other test Infectious colitis due to a bacterial pathogen,
results are shown in Table 1. Stool testing for which is normally a major consideration in a
C. difficile toxin and Shiga toxin was negative, as patient with acute bloody diarrhea, is unlikely to
was examination of the stool for ova and para- account for the months of symptoms seen in
sites; a test for Entamoeba histolytica antibodies this case. Could recurrence of C. difficile infec-
was also negative. A stool specimen was obtained tion, which had been diagnosed during this pa-
for culture. tient’s second admission, explain his entire clini-
Dr. Roller: CT of the abdomen (Fig. 3A and 3B), cal course? Pseudomembranes are not classically
performed after the administration of intrave- seen in patients with recurrent C. difficile disease
nous and oral contrast material, revealed diffuse or inflammatory bowel disease,1 so the absence
bowel-wall thickening and inflammatory changes of pseudomembranes on endoscopic examina-
involving the rectum and the entire colon. There tion does not rule out recurrent infection. How-
was again evidence of calcific atherosclerosis in ever, the clinically significant amount of bleed-
the abdominal aorta and aortic branches, with a ing, the deep colonic ulcerations on endoscopy,
37-mm infrarenal abdominal aortic aneurysm and the absence of fever and leukocytosis are
with mural thrombus. highly unusual for ongoing C. difficile infection.
Dr. Lopes: Treatment with oral vancomycin and There are several parasitic infections to con-
intravenous ganciclovir was started. The patient sider in this case, including E. histolytica and
had bowel movements with bloody stools every Strongyloides stercoralis infections. Intestinal ame-
2 to 3 hours. On the second hospital day, flexible biasis is subacute, with bloody diarrhea lasting
sigmoidoscopy (Fig. 3C and 3D) revealed diffuse weeks to months, and is associated with imag-
severe colonic inflammation, erythema, edema, ing and endoscopic findings that mimic ulcer-
friability, and deep ulcerations in the sigmoid ative colitis, specifically diffuse inflammation,
colon and rectum. friable mucosa, and ulcerations.2 S. stercoralis

colitis is another parasitic infection that can re- patient had a history of vascular disease and a
semble ulcerative colitis,3 and it could account known abdominal aortic aneurysm, and although
for the mild eosinophilia identified at the time his aortic mural thrombus was probably chronic
of this patient’s second hospital admission. and of little clinical relevance, showering of the
Eosinophilia is commonly seen in chronic stron- colonic circulation with cholesterol emboli from
gyloidiasis but not in active disease. In addition, an aortic plaque is possible. Patients with cho-
bandemia, which was noted during this patient’s lesterol embolization most commonly present
third and current hospital admissions, can de- with abdominal pain and bleeding,6 with eosino-
velop when multiplication of colonic larvae dur- philia classically developing during the early
ing the autoinfection stage results in microper- stages.7 However, the absence of involvement of
forations of the bowel. any other organ system, such as the skin or kid-
However, the patient had not been in areas neys, is unusual.
where parasites are endemic. In addition, three Furthermore, the fact that this patient had
features make parasitic colitis an unlikely diag- predominant rectal involvement is not consistent
nosis in this case: the negative laboratory tests, with a vascular insult. The rectum receives its
particularly the negative serologic test for E. histo- blood supply from three distinct sources: the
lytica; the proximal progression of colitis from superior rectal artery, which is a continuation of
the rectum and sigmoid colon, since parasitic the inferior mesenteric artery, the sole blood
entities affect the ascending colon most often supply to the descending colon; the middle rec-
and attenuate distally; and the contiguous in- tal artery, which is a branch of the internal iliac
flammation seen on endoscopic evaluation, since artery; and the inferior rectal artery, which is a
skipped and spared areas are typically seen with branch of the internal pudendal artery. There-
amebiasis and strongyloidiasis.3,4 fore, the rectum is classically spared in a colonic
ischemic event.
Cancer
Gastrointestinal cancer should be considered in Inflammation
patients with chronic lower gastrointestinal blood An inflammatory process is the most likely ex-
loss. In this patient, the features of the clinical planation for this patient’s illness. His history of
presentation and the endoscopic findings make diverticulosis suggests the possibility of seg-
colorectal carcinoma and colonic lymphoma un- mental colitis associated with diverticulosis,
likely. However, plasma-cell dyscrasia and gas- which could account for many of the features
trointestinal amyloidosis can lead to chronic seen in this case, including the persistent bloody
bloody diarrhea.5 The abnormal levels of free diarrhea, abdominal pain, relatively normal lab-
light chains suggest the possibility of amyloido- oratory test results, and erythematous, friable
sis, but this finding by itself is inconclusive and mucosa seen on endoscopic examination. Seg-
could be explained by the patient’s chronic kid- mental colitis associated with diverticulosis in-
ney disease or an alternative inflammatory pro- volves only segments of inflamed colon that are
cess. In addition, this patient did not have any of close to the diverticula, with areas of healthy mu-
the findings associated with amyloidosis, such as cosa interspersed between the inflamed areas.8
heart failure, neuropathy, or proteinuria, nor did The colonic inflammation seen in this patient
he have any histologic findings to support a di- was contiguous. It was also not confined to sec-
agnosis of gastrointestinal amyloidosis. tions in which diverticula were present, such as
the rectum and sigmoid colon; instead, by the
Colonic Ischemia time of the last admission, it spanned the entire
Could this patient’s abdominal pain and bloody colon. Finally, segmental colitis associated with
diarrhea be due to ischemia? Colonic ischemia is diverticulosis spares the rectum, which is an-
manifested by acute, self-limited bloody diarrhea other reason that it cannot account for all the
and is thus unlikely in this case. Given the find- clinical features of this patient’s presentation.
ings on examination of the biopsy specimens of Could another inflammatory condition ac-
the rectum and sigmoid colon, cholesterol crys- count for the patient’s symptoms and explain his
tal embolization should also be considered. This earlier diagnoses of both C. difficile colitis and

CMV colitis? The severe colitis with friable mu-

A
cosa and deep ulcerations on endoscopy, coupled
with the architectural disarray and plasma-cell
deposits on histologic examination, are com-
monly seen in ulcerative colitis. Could this pa-
tient have had underlying ulcerative colitis all
along?
Ulcerative Colitis
C. difficile infection is the infection that is most
commonly associated with inflammatory bowel
disease,9 and it frequently exacerbates the sever-
ity of the disease.10 This patient received cipro-
floxacin, an antibiotic agent associated with the B
development of C. difficile infection. In addition,
there is ample evidence of an association be-
tween CMV colitis and ulcerative colitis. CMV is
frequently found in tissue specimens from pa-
tients with inflammatory bowel disease11;
whether the detection of CMV signifies the pres-
ence of CMV reactivation colitis is a matter of
debate.12 CMV reactivation colitis is common
among patients with ulcerative colitis who are
treated with glucocorticoids.13 CMV colitis is
known to complicate the course of inflamma-
tory bowel disease,14 and testing for CMV is
recommended in patients with worsening ulcer- C
ative colitis, presumably because of the affinity
of CMV for inflamed mucosal surfaces.15 Al-
though the question of whether CMV is involved
in the pathogenesis of ulcerative colitis11,14 or is
an “innocent bystander”16,17 has not been defini-
tively answered, this patient’s initial biopsy re-
sults showing evidence of CMV colitis are con-
sistent with the presence of underlying ulcerative
colitis. Finally, it has been suggested that C. dif-
ficile infection and CMV colitis may occur to-
gether in immunocompetent patients, frequently
with adverse outcomes.18
Ulcerative colitis could account for many Figure 4. Diagnostic Endoscopic Images and Biopsy
other aspects of the patient’s presentation. It is Specimens.
frequently associated with eosinophilia early in Images obtained during flexible sigmoidoscopy per
the disease course and with bandemia as the formed on hospital day 12 (Panels A and B) show se
vere inflammation, congestion, erythema, friability, and
disease progresses, presumably because of un- deep ulcerations (Panel A, arrow) in the rectum and sig
controlled chronic colonic inflammation and moid colon. Hematoxylin and eosin staining of the bi
possible bacterial translocation. Ulcerative coli- opsy specimens (Panel C) shows active chronic colitis
tis is also associated with abnormal immunoglo- with prominent crypt abscesses, which are character
bin levels; although it has traditionally been ized by a collection of neutrophils in the lumen of the
crypts (arrows), features consistent with a diagnosis of
linked to elevated immunoglobin levels, more ulcerative colitis.
recent studies have shown that it may be linked
to low immunoglobulin levels, especially low

IgM levels in older patients.19 The connection markedly active chronic colitis. There was ex-
between ulcerative colitis and an increased risk pansion of the lamina propria by lymphocytes
of thromboembolism is well described20; al- and plasma cells, along with crypt loss and
though the usual concern is an increased risk of patchy surface erosion and ulceration. Neutro-
venous thromboembolism, patients with ulcer- philic inflammation was present in the crypts
ative colitis also have an increased rate of arte- (indicating neutrophilic cryptitis) and in the sur-
rial thrombosis, which could explain in part the face epithelium and lamina propria. Prominent
aortic mural thrombus and the cholesterol em- crypt abscesses were present (Fig. 4C). The dif-
bolization seen in this case. ferential diagnosis included inflammatory bowel
In summary, the chronic bloody diarrhea, the disease, infection, and segmental colitis associ-
development of C. difficile colitis after treatment ated with diverticulosis. Infectious colitis and
with ciprofloxacin, the subsequent admission for inflammatory bowel disease, especially ulcer-
CMV colitis, and the continued clinical deterio- ative colitis, can be similar in histologic appear-
ration with worsening systemic symptoms, ris- ance. However, the prominent crypt abscesses
ing inflammatory markers, and new bandemia, and dense chronic inflammation favor a diagno-
coupled with the endoscopic and histologic find- sis of ulcerative colitis. Segmental colitis associ-
ings, make ulcerative colitis the most likely diag- ated with diverticulosis may be similar in histo-
nosis in this case. logic appearance to ulcerative colitis, and there
may be a relationship between the two entities
in some cases. However, segmental colitis associ-
Cl inic a l Impr e ssion
ated with diverticulosis is usually not as severe
Dr. Lopes: Given this patient’s long-term, relaps- and is limited to areas of diverticular disease; in
ing course of illness, the circumferential and light of these factors, ulcerative colitis is again
contiguous ulceration on sigmoidoscopy, and the the favored diagnosis in this case.
findings suggestive of chronic inflammation on The previous colonic insults — including
biopsy, we thought that the most likely diagnosis documented C. difficile colitis, CMV infection,
was ulcerative colitis. We thought that C. difficile diverticulosis, and probable ischemia — may
colitis was unlikely, given the negative stool have played a role in the development of symp-
tests. We thought that CMV colitis was unlikely tomatic ulcerative colitis.21,22 Alteration of the
to explain the current admission, given the ab- flora in association with mucosal injury and
sence of previous glucocorticoid therapy, the antigen exposure may have thereby altered the
negative viral staining and culture of colonic colonic immune response and stimulated a new
tissue, and the fact that refractoriness to appro- or smoldering autoimmune reaction.
priate CMV therapy is uncommon. To establish
the diagnosis, we performed repeat sigmoidos- Pathol o gic a l Di agnosis
copy (Fig. 4A and 4B) to obtain additional tissue
specimens. Ulcerative colitis.
Cl inic a l Di agnosis Discussion of M a nagemen t

Ulcerative colitis. Dr. Ashwin N. Ananthakrishnan: The onset of in-
flammatory bowel disease traditionally occurs
during young adulthood, but patients older than
Dr . H acho B . Bohossi a n’s
Di agnosis 65 years of age represent a growing fraction of
all patients with inflammatory bowel disease,
Ulcerative colitis. accounting for up to 15% of patients with new
diagnoses and an even greater percentage of
patients who are hospitalized for the condi-
Pathol o gic a l Discussion
tion.23,24 The likelihood that competing diagno-
Dr. Zukerberg: Histologic examination of the third ses — such as infection, ischemic colitis, and
set of biopsy specimens showed evidence of cancer — will be present is higher in this popu-

lation than among younger patients, and there- plays an important pathogenic role in patients
fore, it is important to retain a high index of with severe or therapy-refractory ulcerative coli-
suspicion for inflammatory bowel disease in a tis.16,35,36 Up to one third of patients with acute
patient with relevant clinical features, since severe ulcerative colitis that is refractory to glu-
timely endoscopic investigation is essential to cocorticoids have superimposed CMV colitis.16 In
establish a diagnosis and reduce diagnostic de- such cases, diagnosis of CMV colitis requires
lay.23 Although some studies suggest that the biopsy of the inflamed colon, since blood tests
disease course may be milder in older patients that detect viremia do not have sufficient sensitiv-
because of immunosenescence,25,26 others con- ity and specificity for the diagnosis of gastroin-
clude that older patients with inflammatory testinal disease. Among patients with ulcerative
bowel disease, particularly ulcerative colitis, are colitis who have a response to glucocorticoids,
more likely to undergo surgery within 1 year the benefit of CMV treatment for low-level vire-
after diagnosis, the period of the most unstable mia or a low burden of infection in the colon
disease activity.27,28 remains to be established.35-38 However, among
patients with glucocorticoid-refractory ulcerative
Acute Severe Ulcerative Colitis colitis or a high burden of colonic inflamma-
In up to one third of patients with ulcerative tion, timely initiation of antiviral therapy is ef-
colitis, a fulminant presentation known as acute fective in 75 to 100% of patients.16,36,39,40
severe ulcerative colitis develops at a median of
14 months after diagnosis, leading to hospital- Fol l ow-up
ization for the administration of intravenous
glucocorticoids. The first step in the manage- Dr. Lopes: Once the diagnosis of ulcerative colitis
29
ment of acute severe ulcerative colitis is the ini- was established in this case, intravenous gluco-
tiation of intravenous glucocorticoid therapy, but corticoid therapy was started. Vancomycin and
up to one third of affected patients do not have ganciclovir were discontinued. Inflammatory
an adequate clinical response and receive rescue markers decreased. However, the patient contin-
therapy with either infliximab or cyclosporine.30 ued to have bowel movements every 2 to 3 hours,
Early, objective assessment of response, with accompanied by intermittent bloody stools. He
initiation of rescue therapy within 3 to 5 days in had limited mobility, and anorexia worsened. He
patients who do not have a response, is the pre- was thought to be too frail to undergo surgery.
ferred approach.31 Among patients with ulcera Infliximab therapy was considered, but unfortu-
tive colitis who need emergency hospitalization, nately, aspiration pneumonia developed and the
a delay in surgery is associated with worsened patient’s clinical condition deteriorated. Because
outcomes.32 Although older patients with coex- he had active infection, infliximab infusion was
isting conditions may have an increased baseline withheld. Given the patient’s frailty, severity of
risk of infection, the risk associated with the use illness, and limited therapeutic options, his care
of immunosuppressive therapies as compared was transitioned to comfort measures only. He
with placebo is not greater in this population died on hospital day 22 while sleeping.
than among younger patients. Furthermore, ap-
propriate initiation of effective therapy is impor- A nat omic a l Di agnosis
tant in older patients with inflammatory bowel
disease, since the alternatives of persistent dis- Ulcerative colitis.
ease activity and long-term glucocorticoid use
This case was presented at the Medical Case Conference.
may themselves confer an increased risk of in- Dr. Ananthakrishnan reports receiving grant support from
fection and of death. 33,34
Pfizer and consulting fees from Kyn Therapeutics. No other
Although the role of CMV infection in pa- potential conflict of interest relevant to this article was re-
ported.
tients with ulcerative colitis is debated, it has Disclosure forms provided by the authors are available with
become increasingly clear that CMV infection the full text of this article at NEJM.org.

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The n e w e ng l a n d j o u r na l of m e dic i n e

Case Records of the Massachusetts General Hospital

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Table 1. Laboratory Data.*

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A Figure 1. CT Scans of the Abdomen and Pelvis

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CMV colitis? The severe colitis with friable mu-

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