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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2867_Библиотеки_им_академика_М_И_Перельмана.pdf
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A. Foster
time, COVID-19 testing was less widely available, and many patients were diagnosed and treated based on clinical ndings alone. CT of the chest was consistent
with the diagnosis of COVID-19 pneumonia. The patient had no typical signs or
symptoms of pheochromocytoma. Importantly, the patient satised the criteria for
acute heart failure with elevated pro-BNP and decreased ejection fraction in the setting of meeting criteria for NSTEMI (elevated troponin, ST deviation on ECG, and
segmental wall motion abnormalities on the echocardiogram). COVID-19 has been
reported as a potential trigger for myocardial infarction, which is in line with an
already relatively well-established link between COVID-19 and thrombosis development [10, 11]. Under those assumptions, the patient was placed on the appropriate treatment at the time, including supportive management of COVID-19,
broad-spectrum antibiotics due to leukocytosis, and aspirin and anticoagulation.
Myocardial infarction can lead to acute heart failure, which can also lead to pulmonary edema. Once COVID-19 was ruled out by two consecutive negative PCR tests,
the case became even more complicated. The patient’s symptoms remained nonspecic and only consistent with heart failure without much clinical evidence of an
underlying pheochromocytoma. Mild intermittent tachycardia (present on the initial
physical exam but not on the EKG) could have been explained by sympathetic activation due to decreased ejection fraction. Improvement in lung imaging was attributed to pneumonia treatment, although it is questionable whether radiological
ndings of pneumonia would have disappeared over a period of 1 week, even with
the resolution of the infection itself. Pheochromocytoma was diagnosed incidentally because the patient started complaining of abdominal discomfort, which could
have been related either to the tumor itself or to worsening volume overload in the
setting of heart failure with reduced ejection fraction.
Therefore, an abdominal CT scan was ordered. Even though, as previously
explained, pheochromocytoma is a possible cause of heart failure, a pheochromocytoma workup is not typically undertaken when a patient presents with signs and
symptoms of heart failure. That means that, in the absence of symptoms which
would trigger an appropriate workup, cases of pheochromocytoma-induced heart
failure with minimal obvious hyperadrenergic ndings are likely to be diagnosed
late. Once the adrenal tumor was found, endocrine studies were ordered to determine its etiology, and nally, a pathological diagnosis was made after surgical
resection. The etiology of the tumor itself remains unclear, although, in the literature, there are reports of pheochromocytoma being triggered by COVID-19 [12].
Conclusion
Even if a disease is highly prevalent in the population at the time, it is important not
to jump to conclusions and label patients with the diagnosis prematurely. Moreover,
cases of acute heart failure of unknown etiology, especially in a younger patient,
should prompt a more thorough workup. We believe that it is not unreasonable to
obtain urine metanephrines in individuals with sudden onset acute heart failure even
24 Pheochromocytoma Misdiagnosed asCOVID-19
161
without obvious signs of elevated catecholamines since the test is simple and relatively inexpensive and may detect cases that would otherwise remain undiagnosed
until it is too late.
References
1. Reisch N, Peczkowska M, Januszewicz A, Neumann HP. Pheochromocytoma: presentation, diagnosis and treatment. J Hypertens. 2006;24(12):2331–9. https://doi.org/10.1097/01.
hjh.0000251887.01885.54.
2. Ram CV.Pheochromocytoma. Cardiol Clin. 1988;6(4):517–35.
3. Farrugia FA, Charalampopoulos A.Pheochromocytoma. Endocr Regul. 2019;53(3):191–212.
https://doi.org/10.2478/enr- 2019- 0020.
4. Cornu E, Motiejunaite J, Belmihoub I, Vidal-Petiot E, Mirabel M, Amar L.Acute stress cardiomyopathy: heart of pheochromocytoma. Ann Endocrinol (Paris). 2021;82(3–4):201–5.
https://doi.org/10.1016/j.ando.2020.03.011.
5. Zhang R, Gupta D, Albert SG.Pheochromocytoma as a reversible cause of cardiomyopathy:
analysis and review of the literature. Int J Cardiol. 2017;249:319–23. https://doi.org/10.1016/j.
ijcard.2017.07.014.
6. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review.
JAMA. 2020;324(8):782–93. https://doi.org/10.1001/jama.2020.12839.
7. Mele D, Flamigni F, Rapezzi C, Ferrari R.Myocarditis in COVID-19 patients: current problems. Intern Emerg Med. 2021;16(5):1123–9. https://doi.org/10.1007/s11739- 021- 02635.
8. Siripanthong B, Nazarian S, Muser D, et al. Recognizing COVID-19-related myocarditis:
the possible pathophysiology and proposed guideline for diagnosis and management. Heart
Rhythm. 2020;17(9):1463–71. https://doi.org/10.1016/j.hrthm.2020.05.001.
9. Cooper LT Jr. Myocarditis. N Engl J Med. 2009;360(15):1526–38. https://doi.org/10.1056/
NEJMra0800028.
10. Ali MAM, Spinler SA.COVID-19 and thrombosis: from bench to bedside. Trends Cardiovasc
Med. 2021;31(3):143–60. https://doi.org/10.1016/j.tcm.2020.12.004.
11. Sharma A, Matta A, Matta D, Bande D. Non-ST segment elevation myocardial infarction secondary to coronary multi-vessel thrombosis in the setting of COVID-19. Cureus.
2021;13(11):e19258. https://doi.org/10.7759/cureus.19258.
12. Naghshineh H, Hasanpour A, Ziaei N, Sadeghi M, Meftah N.Pheochromocytoma triggered
by coronavirus disease 2019: a case report. J Med Case Rep. 2022;16(1):233. https://doi.
org/10.1186/s13256- 022- 03378- 8.
Part V
Gastroenterology
Chapter 25
Initial Misdiagnosis ofCeliac Disease
withLife-Threatening Presentation
AnthonyV.Baratta Jr.
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Discuss the variable presentations of celiac disease.
2. Recognize those at increased risk for celiac disease.
3. Create a differential diagnosis for celiac disease and celiac crisis.
4. Review the challenges in accurately diagnosing celiac disease.
5. Recognize the common and uncommon complications of celiac disease.
Introduction
Celiac disease is an immune-mediated illness precipitated by ingestion of gluten in
genetically susceptible individuals [1, 2]. It is a disorder of the small intestine, characterized by villous atrophy and mucosal inammation, with improvement following withdrawal of gluten from the diet. Note celiac disease differs from non-celiac
gluten sensitivity, in which symptomatic improvement off gluten is not associated
with histologic or serologic evidence of celiac disease.
Over 98% of individuals with celiac disease have the human leukocyte antigen
(HLA) DR3-DQ2 and/or DR4-DQ8, compared with 30–40% of the general population of most developed nations [3, 4]. In patients with celiac disease, the immune
response to gliadin promotes inltration of chronic inammatory cells in the lamina
propria, progressing to villous atrophy. The inammatory cascade triggers the
release of tissue transglutaminase from endothelial cells and broblasts.
A. V. Baratta Jr. (*)
Gastroenterology Associates of Rochester, Rochester, NY, USA
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
H. Tohid et al. (eds.), The Misdiagnosis Casebook in Clinical Medicine,
https://doi.org/10.1007/978-3-031-28296-6_25
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A. V. Baratta Jr.
Transglutaminase deamidation of gluten peptides potentiates stimulation of T
cells [5, 6].
The estimated prevalence of celiac disease is approximately 1% in most countries, based primarily on serologic studies [7, 8]. The known cases of celiac disease
may represent only the tip of the iceberg, as suggested by population-based studies.
Those without symptoms may account for symptomatic individuals by a ratio of
7:1. Moreover, the prevalence of celiac disease has been gradually increasing over
the past several decades [9–12]. High-risk groups for celiac disease include rstand second-degree relatives, along with Down syndrome and several autoimmune
disorders (autoimmune thyroid disease, type 1 diabetes mellitus) [13, 14].
The clinical presentation of celiac disease is variable, ranging from asymptomatic patients to those with profound malabsorption [15]. Classic presenting features
may include diarrhea with malodorous oating stools, from steatorrhea. Other
symptoms may include abdominal pain, bloating, and even constipation.
Consequences of malabsorption may include weight loss and iron deciency anemia, along with deciency of B vitamins. Extraintestinal manifestations may
include elevated liver enzymes, recurrent headaches, fatigue, dermatitis herpetiformis, reduced fertility, peripheral neuropathy, dental enamel hypoplasia, osteoporosis, aphthous stomatitis, and cerebellar ataxia. Rarely, patients may initially present
with “celiac crisis,” characterized by acute large volume diarrhea, dehydration, and
metabolic disturbances. Complications may include neuromuscular weakness, seizures, and potentially fatal arrhythmias [16].
It is important for clinicians to recognize both the typical and atypical presentations of celiac disease in order to arrive at a timely diagnosis. This is important both
to improve quality of life as well as to minimize potentially serious complications
of untreated celiac disease. Prior to availability of serologic testing and endoscopic
biopsy, individuals with celiac disease often suffered consequences of misdiagnosis
or lengthy delays in diagnosis. Testing for celiac disease is most accurate when
patients are on a diet containing gluten. Those considered at low risk for celiac disease should rst undergo serologic testing. The serum tissue transglutaminase test
(tTG-IgA) is most commonly used, along with measurement of total IgA levels (as
those with IgA deciency require IgG celiac antibody serology testing). Those with
positive transglutaminase serology should undergo upper endoscopy with biopsies
of the proximal small intestine. Negative serology results often have a high negative
predictive value in those at low risk for celiac disease, such that endoscopy in those
individuals can be avoided.
Individuals with a high probability of celiac disease may include those with typical symptoms as outlined above, along with those having signicant risk factors.
Individuals with high probability should undergo both serologic testing and upper
endoscopy with duodenal biopsies. Celiac disease is conrmed when positive serology is combined with abnormal duodenal biopsies, typically villous atrophy. Those
with mucosal inammation (increased intraepithelial lymphocytes) but normalappearing villi may require close monitoring with consideration of repeat endoscopy months or several years later.
25 Initial Misdiagnosis ofCeliac Disease withLife-Threatening Presentation
167
Testing for HLA DQ 2 and HLA DQ8 may be helpful in equivocal cases, especially those on a long-term gluten-free diet. Some individuals already avoiding
gluten may be unwilling to undergo a gluten challenge. Negative testing for both
HLA DQ 2 and HLA DQ8 helps to exclude celiac disease with at least 98%
accuracy.
Multiple biopsies from the duodenum are recommended for conrming celiac
disease. Histologic features may range from an increase in intraepithelial lymphocytes to severe villous atrophy with crypt hyperplasia. The Marsh classication is
often used to grade histologic severity.
Clinical Case Presentation
Presenting to the emergency department is a 34-year-old female with over 2 weeks
of severe diarrhea (7–10 stools per day) along with weakness of extremities,
accompanied by weight loss of 22 pounds over 2 months. She reported taking oral
iron supplementation. Physical examination revealed severe muscle weakness
involving all extremities, along with a positive Trousseau’s sign. The patient’s
vital signs were assessed and within normal range, and the abdominal exam was
unremarkable. Electrocardiogram revealed sinus rhythm, attened T waves along
with U waves, type 1 atrioventricular block, and QTc prolongation. Laboratory
testing revealed profound electrolyte disturbances, including severe hypokalemia
(1.6mmoL per L), severe hypocalcemia (0.9mmoL/L ionized), hypomagnesemia
(1.6 mmol/L), and hypophosphatemia (1.6 mg/dL). Complete blood count
revealed hemoglobin of 8.5g/dL and ferritin of 2ng/mL, along with folate deciency (2ng/mL) and hypoalbuminemia (2.6g/dL). She received adequate rehydration along with replacement of potassium and correction of other metabolic
abnormalities. The initial differential included infectious gastroenteritis and acute
onset Crohn’s disease. Stool tests were unremarkable for culture and occult blood.
Abdominal radiograph and ultrasound were unremarkable. Transaminases were
slightly elevated, including aspartate transaminase (60U/L) and alanine transaminase (47U/L). Upper endoscopy eventually was performed to investigate the iron
deciency anemia and weight loss, revealing scalloping of duodenal folds with a
mosaic pattern, and duodenal biopsies revealing severe villous atrophy. Tissue
transglutaminase was mildly elevated at 23U/mL, and IgA endomysial antibody
was elevated (1:80). A diagnosis of celiac disease was made on the basis of the
clinical presentation accompanied by severe villous atrophy and elevated celiac
antibodies. Fortunately, the patient responded to gluten withdrawal, without the
need for steroid therapy (steroids are often considered for celiac crisis). The diarrhea and muscle weakness improved signicantly, and the patient was discharged
1 week after admission [17].
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A. V. Baratta Jr.
Differential Diagnosis
The differential diagnosis in this case includes the following.
1. Infectious enterocolitis—Always needs to be considered in patients presenting
with acute or subacute diarrheal illness, as it is one of the leading causes with
this presentation.
2. Acute onset inammatory bowel disease—May also have a similar atypical
presentation.
3. Celiac crisis—While rare, needs to be entertained given the signicant diarrhea
and weight loss along with laboratory features of malabsorption.
4. Microscopic colitis—Sometimes associated with celiac disease.
5. Ischemic colitis—May cause diarrhea and cramps, sometimes with bleeding,
more often in older individuals. Ischemic colitis may occur in younger patients
as well, related to coagulation disorders or medication-induced bowel ischemia.
6. Medication-induced diarrhea.
7. Carcinoid syndrome—While rare, may cause a subacute presentation of a secre-
tory diarrhea, usually accompanied by ushing.
8. Intestinal tuberculosis—Rare but may sometimes mimic Crohn’s, with diarrhea
and abdominal pain accompanied by fever and other constitutional manifestations. Risk factors include impaired immunity and exposure to infectious
persons.
9. Amebiasis—Affected individuals in developed nations often report recent travel
to endemic areas.
What WasMisdiagnosed inThis Case andWhy?
The possibility of celiac crisis was not initially considered in this patient. Rather,
infectious enteritis and inammatory bowel disease were considered higher in the
differential, as they are more commonly encountered than acute celiac crisis.
Discussion
It is important to consider the variable presentations of celiac disease in order to
make a prompt diagnosis, with appropriate management. The classic presentation
for celiac disease may include chronic diarrhea with bloating, malodorous stools,
and modest weight loss. However, many individuals do not present with classic,
typical features. Other important presentations may include iron deciency anemia,
constipation, recurrent headaches, and recurrent fetal loss.
Atypical and extraintestinal manifestations include unexplained elevation in
serum transaminases, dermatitis herpetiformis, B12 deciency, aphthous stomatitis,
25 Initial Misdiagnosis ofCeliac Disease withLife-Threatening Presentation
169
premature osteoporosis, dental enamel hypoplasia, peripheral neuropathy, and cerebellar ataxia [18, 19].
Individuals at increased risk for celiac disease may include rst and seconddegree relatives, Down syndrome, autoimmune thyroiditis, and type 1 diabetes mellitus. Practitioners should consider testing for celiac disease in any of these clinical
scenarios.
Clinicians are more likely to consider testing for symptomatic celiac disease in
those with chronic diarrhea rather than acute diarrhea. In our case presentation, the
acute/subacute presentation was not typical of celiac disease. However, clues in this
patient suggesting celiac disease included persistent diarrhea with weight loss, iron
deciency anemia, transaminase elevation, and signicant metabolic disturbances
(as may occur with severe malabsorption).
Late diagnosis of celiac disease was not unusual many decades ago, prior to the
availability of endoscopy (with duodenal biopsies) and prior to currently available
serologic tests for celiac disease. Indeed, the two most important tests for diagnosing celiac disease include abnormal duodenal histology and serology. An assured
diagnosis can be made in the presence of high titer transglutaminase levels combined with villous atrophy. However, it is important to appreciate a spectrum exists,
such that a diagnosis is often challenging with minimally elevated celiac antibodies
and/or with minimally abnormal histology. Relative to these cases, one must also
consider the clinical presentation and the response to gluten withdrawal, along with
family history, HLA testing, and consideration of follow-up testing (repeating
endoscopy/biopsy and obtaining additional serology such as anti-endomysial antibodies and/or deamidated gliadin peptides). These measures may help improve the
accuracy for diagnosing celiac disease [20].
While misdiagnosis of medical conditions often refers to delayed or incorrect
diagnoses, the potential for “overdiagnosis” is often under-recognized and underappreciated. At a tertiary referral center in Italy, of 614 patients diagnosed with celiac
disease at other institutions, only 70% were able to be conrmed. The remaining
30% did not have a combination of villous atrophy and abnormal serology and were
determined not to have celiac disease [21]. Many had other diagnoses (Crohn’s
disease, irritable bowel syndrome, microscopic colitis) and were unnecessarily following a gluten-free diet without clinical benet.
All patients with conrmed celiac disease should adhere to a gluten-free diet.
There are several important components of managing celiac disease, including the
following: education about celiac disease, consultation with a skilled dietitian, lifelong adherence to a gluten-free diet, identication and management of nutritional
deciencies, access to a celiac support group, and long-term follow-up by a multidisciplinary team.
Fortunately, online and other educational resources for celiac disease are much
more extensive today than existed several decades ago. The biggest challenge for
those with celiac disease is strict lifelong adherence to a gluten-free diet. Local and
online support groups may be extremely helpful, both for dietary advice and emotional support.
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Affected patients should also meet with a registered dietitian who is knowledgeable regarding celiac disease. The primary components of dietary gluten include
wheat, rye, and barley. Dietitians can provide instructions for basic dietary modication, along with suggestions for minimizing inadvertent gluten ingestion.
The response to dietary gluten is extremely variable among patients. While some
are asymptomatic, others are sensitive to minute amounts of gluten. Rare patients
may be at risk for celiac crisis, as in our case presentation.
Risks of untreated celiac disease may include iron deciency anemia, micronutrient deciency, metabolic abnormalities, osteoporosis, other autoimmune disorders, and increased risk for malignancy (including lymphoma and gastrointestinal
cancers).
Plan ofAction
Recognize both the typical and atypical presentations of celiac disease. Appreciate
how celiac crisis may present as a severe atypical infectious gastroenteritis, with
potentially fatal outcome if misdiagnosed. Consider transglutaminase testing more
often in these clinical settings, including the various presentations outlined above.
Conclusion
Celiac disease is a small bowel disorder with villous atrophy induced by exposure
to gluten and improved with withdrawal of gluten from the diet. Testing should be
performed for those with gastrointestinal or extraintestinal manifestations of celiac
disease. While evaluation often begins with transglutaminase serology, upper
endoscopy and small bowel biopsy usually are necessary for conrmation and accurate diagnosis. Clinicians should appreciate both the classic and atypical presentations of celiac disease.
References
1. Kagnoff MF, Celiac disease. A gastrointestinal disease with environmental, genetic, and
immunologic components. Gastroenterol Clin N Am. 1992;21:405.
2. Schuppan D.Current concepts of celiac disease pathogenesis. Gastroenterology. 2000;119:234.
3. Pietzak MM, Schoeld TC, McGinniss MJ, Nakamura RM.Stratifying risk for celiac disease
in a large at-risk United States population by using HLA alleles. Clin Gastroenterol Hepatol.
2009;7:966.
4. Liu E, Lee HS, Aronsson CA, etal. Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med. 2014;371:42.
25 Initial Misdiagnosis ofCeliac Disease withLife-Threatening Presentation
5. Molberg O, Mcadam SN, Körner R, etal. Tissue transglutaminase selectively modies gliadin
peptides that are recognized by gut-derived T cells in celiac disease. Nat Med. 1998;4:713.
6. van de Wal Y, Kooy Y, van Veelen P, etal. Selective deamidation by tissue transglutaminase
strongly enhances gliadin-specic T cell reactivity. J Immunol. 1998;161:1585.
7. Gujral N, Freeman HJ, Thomson AB.Celiac disease: prevalence, diagnosis, pathogenesis and
treatment. World J Gastroenterol. 2012;18:6036.
8. Singh P, Arora A, Strand TA, etal. Global prevalence of celiac disease: systematic review and
meta-analysis. Clin Gastroenterol Hepatol. 2018;16:823.
9. Rubio-Tapia A, Ludvigsson JF, Brantner TL, etal. The prevalence of celiac disease in the
United States. Am J Gastroenterol. 2012;107:1538.
10. Catassi C, Fabiani E, Rätsch IM, etal. The coeliac iceberg in Italy. A multicentre antigliadin antibodies screening for coeliac disease in school-age subjects. Acta Paediatr Suppl.
1996;412:29.
11. Fasano A, Berti I, Gerarduzzi T, etal. Prevalence of celiac disease in at-risk and not-at-risk
groups in the United States: a large multicenter study. Arch Intern Med. 2003;163:286.
12. Gatti S, Lionetti E, Balanzoni L, etal. Increased prevalence of celiac disease in school-age
children in Italy. Clin Gastroenterol Hepatol. 2020;18:596.
13. Kahaly GJ, Frommer L, Schuppan D.Celiac disease and endocrine autoimmunity—the genetic
link. Autoimmun Rev. 2018;17:1169.
14. Singh P, Arora S, Lal S, etal. Risk of celiac disease in the rst- and second-degree relatives
of patients with celiac disease: a systematic review and meta-analysis. Am J Gastroenterol.
2015;110:1539.
15. West J, Logan RF, Hill PG, Khaw KT.The iceberg of celiac disease: what is below the waterline? Clin Gastroenterol Hepatol. 2007;5:59.
16. Jamma S, Rubio-Tapia A, Kelly CP, et al. Celiac crisis is a rare but serious complication of
celiac disease in adults. Clin Gastroenterol Hepatol. 2010;8:587.
17. Guarino M, Gambuti E, Alfano F, etal. Life-threatening onset of coeliac disease: a case report
and literature review. BMJ Open Gastroenterol. 2020;0:e000406. https://doi.org/10.1136/
bmjgast- 2020- 000406.
18. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening
for celiac disease: US preventive services task force recommendation statement.
JAMA. 2017;317:1252.
19. Rubio-Tapia A, Hill ID, Kelly CP, etal. ACG clinical guidelines: diagnosis and management
of celiac disease. Am J Gastroenterol. 2013;108:656.
20. Husby S, Murray JA, Katzka DA. AGA clinical practice update on diagnosis and monitoring of celiac disease-changing utility of serology and histologic measures: expert review.
Gastroenterology. 2019;156:885.
21. Biagi F, Bianchi PI, Campanella J, Zanellati G, Corazza GR.The impact of misdiagnosing
celiac disease at a referral centre. Can J Gastroenterol. 2009;23(8):543–5.
171