Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2867_Библиотеки_им_академика_М_И_Перельмана.pdf
6
It is most common in children and patients with a history of atopy, family history, obesity, or smoking. Presenting symptoms include wheezing, productive
cough, chest tightness, and dyspnea. Chest imaging may be normal, but
pulmonary function tests are the mainstay of diagnosis. First-line treatment is
with inhaled beta-2 agonists.
K. Kar pinska-Leydier
What WasMisdiagnosed inThis Case andWhy?
Serologic allergic bronchopulmonary aspergillosis (ABPA-S) was misdiagnosed as
recurrent bacterial pneumonia after a nonspecic clinical presentation and sequelae
before a bronchoalveolar lavage conrmed the presence of Aspergillus.
Discussion
Nonspecic clinical presentations, such as a productive cough with pulmonary inltrates on imaging, often obtain an initial diagnosis based on disease prevalence
within a population. Cases of ABPA are considered rare and often mistaken for
either bacterial pneumonia or pulmonary TB [1]. The estimated prevalence of ABPA
in asthma and CF patients is 1–2% and 2–9%, respectively; however, rarer cases
may occur in lung transplant recipients or other coexisting disorders, including
hyper-IgE syndrome and chronic granulomatous disease [11]. ABPA is the leading
cause of pulmonary fungal pathology but maintains a high rate of misdiagnosis
[11]. However, diagnostic algorithms targeted to the most accurate and sensitive
diagnostic criteria could alter the prevalence of ABPA; nevertheless, a simple periodic screening in patients with asthma for skin prick testing of Aspergillus-specic
IgE may be sufcient in some instances [11–13].
The chosen case describes a patient diagnosed with bacterial pneumonia [1].
Antibiotic treatment resulted in an initial improvement followed by recurrence of
productive cough and worsening condition; this is typical in the misdiagnosis of
allergic bronchopulmonary aspergillosis (ABPA) [1]. Eosinophilia was conrmed;
however, Klebsiella pneumoniae, isolated from sputum, appeared to conrm the
initial diagnosis, and the patient continued with antibiotic treatment [1]. Despite a
negative skin prick test, total serum IgE and specic IgG to Aspergillus were posi-
tive [1]. However, it was not until a bronchoscopy showing mucous plugging and
culture from bronchoalveolar lavage (BAL) that serologic ABPA (ABPA-S) was
conrmed [1].
It is common for patients in TB endemic areas to undergo multiple courses of TB
treatment regimens even if acid-fast bacteria testing is negative [14]. A study in
Nepal showed that 40% of ABPA patients are misdiagnosed and treated for TB
despite eosinophilia and high total serum IgE [15]. In some instances, a high total
IgE and positive anti-Aspergillus IgE and IgG antibodies may be found but not
1 Allergic Bronchopulmonary Aspergillosis Masquerading as Recurrent Bacterial…
7
recognized as clinically signicant due to the low prevalence of ABPA [14]. Patients
may present with mediastinal lymphadenopathy suggesting TB; however, ABPA
should be considered and not ruled out based on this nding. Further overlap of
features between ABPA and TB may include miliary mottling. In these settings,
subtleties of eosinophilia should prompt vigilance in ABPA investigation [16].
Among patients with chronic or idiopathic bronchiectasis, many are sensitized to
Aspergillus fumigatus or have a sputum culture supporting ABPA [17]. An allergic
background, most commonly with asthma, is a predisposing factor for ABPA,
although not always necessary [10].
Antibiotic therapy may lead to an initially favorable clinical and radiologic
response, further masking a fungal cause, and the presence of a bacterial coinfection, as seen in this case, may further distract from diagnostic accuracy. This
patient was ultimately treated with high-dose inhaled steroids; relevant medical history precluded the use of systemic corticosteroids. The patient had signicant clinical improvement with remission of the CXR lesions and a normal eosinophil count
[1]. ABPA is a hypersensitivity reaction more common in atopic patients or those
with underlying lung pathology such as CF; however, patients without a history of
asthma are susceptible [18]. Skin prick testing to A. fumigatus has a sensitivity of
90%, but the demonstration of specic IgE has a sensitivity of 100% [19]. In this
case, the skin prick testing was negative [1]. A lack of standardized testing and
improper technique regarding skin prick testing may contribute to missed clinical
recognition [18]. Overlapping features and low prevalence contribute to the easy
misdiagnosis of ABPA. Patients with asthma and pulmonary CF should be under
careful consideration for ABPA, especially with new-onset wheezing, sputum, eeting inltrations, or elevated eosinophils [20].
Conclusion
ABPA is an allergic hypersensitivity to a species of fungus, most commonly
Aspergillus fumigatus which is generally considered rare but most commonly occurs
in patients with asthma or CF.Many of the clinical features of ABPA overlap with
bronchopulmonary pneumonia and TB.The rarity of ABPA and ambiguity of clinical presentation contribute to widespread misdiagnosis. Close attention to eosinophilia, specic and total IgE, and skin prick testing standardization are proposed to
improve the accurate and early diagnosis of ABPA.High-risk patients with a history
of allergy or asthma, immunocompromised, or structural lung pathologies require
particular vigilance for ABPA in the presence of Aspergillus sensitization and newonset or worsening pulmonary symptoms.
8
K. Kar pinska-Leydier
References
1. Le Thuong V, Nguyen Ho L, Tran VN.Allergic bronchopulmonary aspergillosis masquerading
as recurrent bacterial pneumonia. Med Mycol Case Rep. 2016;12:11–3. Published 2016 Jun
27. https://doi.org/10.1016/j.mmcr.2016.06.004.
2. Singh B, Singh S, Asif A, Oellerich M, Sharma G. Allergic aspergillosis and the antigens
of aspergillus fumigatus. Curr Protein Peptide Sci. 2014;5:403–23. https://doi.org/10.217
4/1389203715666140512120605.
3. Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax.
2014;3:270–7. https://doi.org/10.1136/thoraxjnl- 2014- 206291.
4. Al-Moudi. Allergic bronchopulmonary aspergillosis mimicking pulmonary tuberculosis.
Saudi Med J. 2001;22:708–13.
5. Mou Y, Ye L, Ye M, Yang D, Jin M.A retrospective study of patients with a delayed diagnosis of allergic bronchopulmonary aspergillosis/allergic bronchopulmonary mycosis. Allergy
Asthma Proc. 2014;2:192–2. https://doi.org/10.2500/aap.2014.35.3731.
6. Shah A. Allergic bronchopulmonary aspergillosis: an Indian perspective. Curr Opin Pulm
Med. 2007;1:72–80. https://doi.org/10.1097/mcp.0b013e328011a284.
7. Iqbal N, Amir Sheikh MD, Jabeen K, Awan S, Irfan M.Allergic bronchopulmonary aspergillosis misdiagnosed as smear negative pulmonary tuberculosis; a retrospective study from
Pakistan. Ann Med Surg. 2021;72:103045. https://doi.org/10.1016/j.amsu.2021.103045.
8. Zeng Y, Xue X, Cai H, et al. Clinical characteristics and prognosis of allergic bronchopulmonary aspergillosis: a retrospective cohort study. J Asthma Allerg. 2022;Volume 15:53–62.
https://doi.org/10.2147/jaa.s345427.
9. Zou MF, Li S, Yang Y, et al. Clinical features and reasons for missed diagnosis of allergic
bronchopulmonary aspergillosis. Zhonghua yi xue za zhi. 2019;99(16):1221–5. https://doi.
org/10.3760/cma.j.issn.0376- 2491.2019.16.006.
10. Zhang C, Jiang Z, Shao C.Clinical characteristics of allergic bronchopulmonary aspergillosis.
Clin Respir J. 2020;5:440–6. https://doi.org/10.1111/crj.13147.
11. Ayoubi N, Jalali S, Kapadia N.A case of allergic bronchopulmonary aspergillosis (ABPA) in
a patient with a history of cocaine use and tuberculosis. Case Rep Med. 2019;23:1–4. https://
doi.org/10.1155/2019/3265635.
12. Xia TT, Xu ZB, Liu XZ, etal. New advances in the diagnosis and treatment of allergic bronchopulmonary aspergillosis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2016;38(5):611–6.
https://doi.org/10.3881/j.issn.1000- 503X.2016.05.022.
13. Lou B, Xu Z, Yang G, et al. Role of aspergillus fumigatus-specic IgE in the diagnosis of
allergic bronchopulmonary aspergillosis. Int Arch Allergy Immunol. 2019;4:338–44. https://
doi.org/10.1159/000495365.
14. Mizuhashi K, Fujimura M.A patient with allergic bronchopulmonary aspergillosis (ABPA)
who had undergone tuberculosis treatment twice. Arerugi. 2021;70(4):302–9. https://doi.
org/10.15036/arerugi.70.302.
15. Agarwal N, Shrestha P, Chokhani R. Allergic BronchoPulmonary aspergillosis in Nepal.
JNMA J Nepal Med Assoc. 2014;52(196):1020–3.
16. Singh U, Aneja P, Kaur B, Patel K.Miliary nodules: an unusual presentation of allergic bronchopulmonary aspergillosis. Lung India. 2014;3:285. https://doi.org/10.4103/0970- 2113.135784.
17. Kaur K, Sharma K, Girdhar N, Gupta A, Chopra V.Another rare presentation of allergic
bronchopulmonary aspergillosis. Monaldi Arch Chest Dis. 2021;91 https://doi.org/10.4081/
monaldi.2021.1696.
18. Muthu V, Behera D, Agarwal R. Allergic bronchopulmonary aspergillosis or pulmonary tuberculosis: a case of mistaken identity? Lung India. 2015;5:529. https://doi.
org/10.4103/0970- 2113.164191.
1 Allergic Bronchopulmonary Aspergillosis Masquerading as Recurrent Bacterial…
19. Bahous J, Malo JL, Paquin R, Cartier A, Vyas P, Longbottom JL.Allergic bronchopulmonary
aspergillosis and sensitization to aspergillus fumigatus in chronic bronchiectasis in adults. Clin
Allergy. 1985;15(6):571–9. https://doi.org/10.1111/j.1365- 2222.1985.tb02311.x.
20. Zhang M, Gao J.Clinical analysis of 77 patients with allergic bronchopulmonary aspergillosis in Peking union medical college hospital. Zhongguo Yi Xue Ke Xue Yuan Xue Bao.
2017;39(3):352–7. https://doi.org/10.3881/j.issn.1000- 503X.2017.03.009.
9
Chapter 2
Angioedema Bowel Blockade:
TheMisdiagnosis ofHereditary
Angioedema asaRare Cause ofSmall
Bowel Obstruction
ArseniKhorochkov
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Raise clinical awareness of hereditary angioedema.
2. Familiarize clinicians with the history and presentation of hereditary angioedema.
3. Recommend the use of the “Hereditary AngioEdema Rapid Triage” (HAE-RT)
tool for assessing angioedema.
4. Suggest the addition of C1-INH and C4 levels to the lab analysis in cases of
acute abdominal pain or angioedema swelling with no discernible cause.
5. Appropriately manage patients with HAE to reduce the need for unnecessary
procedures and improve the overall patient quality of life.
6. Apply the knowledge gained from this case presentation to identify and treat
patients with HAE.
Introduction
Acute abdominal pain can have a wide array of differentials. In the case of bowel
obstruction caused by hereditary angioedema (HAE), it easily can be misdiagnosed
as a more common disorder such as gastroenteritis or acute appendicitis [1–6].
Hereditary angioedema (HAE) is an autosomal dominant disorder characterized
by the deciency or dysfunction of complement 1 (C1) inhibitor (C1-INH) [2, 7–
10]. This can eventually lead to episodes of bradykinin-induced non-pitting angio-
edema of subcutaneous and submucosal tissues [7]. In the case of intestinal
submucosal angioedema, it can lead to obstruction of the bowel lumen and
A. Khorochkov (*)
California Institute of Behavioral Neurosciences and Psychology, Faireld, CA, 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_2
11
12
A. Khorochkov
bradykinin- mediated acute abdominal pain that can be easily misdiagnosed as various other more common conditions affecting the abdomen [2, 3]. Due to the eclectic
nature of the HAE episodes, symptoms can have a wide array of differentials [1, 2].
Physicians unfamiliar with HAE or the patient’s medical history may then proceed
to treat the patient improperly and may subject them to unnecessary surgical procedures such as appendectomy, exploratory laparotomy, or hysterectomy [2, 4, 8, 11].
The angioedema of HAE can occur in the subcutaneous regions of the face, upper
and lower extremities, and genitalia, and the submucosa commonly involved is the
respiratory and gastrointestinal tracts. Although painful abdominal manifestations
are the most common, it is essential to note that in the respiratory tract, laryngeal
swelling may occur and is an emergency as it can be fatal due to asphyxiation [7, 8,
11]. These angioedema episodes can be triggered by physical stressors (e.g., trauma,
infection, surgical procedures, etc.) and emotional stressors [11, 12].
Other known triggers include certain medications and hormonal changes; however, episodes can also be triggered idiopathically [11, 12]. If left untreated, the
swelling can usually last up to 5days before beginning to resolve [7]. Since this is
bradykinin-mediated angioedema, treatment typically involves antagonism of bradykinin receptors or reduction of bradykinin production [7, 13]. In the clinical setting, angioedema is commonly caused by the mast cell-mediated type and, as such,
is treated with antihistamines, glucocorticoids, and epinephrine [3, 13]. However,
these treatments are ineffective in the treatment of the bradykinin variant [3, 13].
Clinical Case Presentation
In this case, a 52-year-old man presented to the surgery department with a 2-day
history of acute abdominal pain. The pain was gradual and located in the right upper
quadrant (RUQ), epigastric, and central abdominal regions. The patient reported
three episodes of vomiting the day before presenting and constipation and lack
of atus.
The patient’s medical history includes hereditary angioedema (HAE), an open
appendectomy in his youth, and hypercholesterolemia. His family history includes
HAE and myocardial infarction on his paternal side. His current medications are
danazol, a mild androgen as prophylaxis for his HAE, and atorvastatin for
hypercholesterolemia.
Upon examination, the patient was alert, oriented, afebrile, and normotensive.
Tenderness was present in the RUQ, epigastric, and paraumbilical regions. Bowel
sounds were decreased, and Murphy’s sign was negative. The patient’s urinalysis
showed a minor elevation in amylase (938U/L) and C-reactive protein (17.3mg/L).
His complete blood count (CBC), liver function test (LFT), electrolytes, and urea
levels were normal. The chest X-ray was noncontributory, and the abdominal X-ray
showed the presence of air-uid level and a visible jejunal loop. A contrast
2 Angioedema Bowel Blockade: The Misdiagnosis of Hereditary Angioedema as…
13
computed tomography (CT) scan of the abdomen and pelvis indicated proximal and
mid-small bowel obstruction, circumferential thickening with edema of the distal
ileum, and sigmoid diverticulosis, but no signs of diverticulitis. There was a modest
amount of free uid in the abdomen and pelvis but no signs of free air. The initial
differential diagnoses pointed towards acute pancreatitis or acute cholecystitis and
bowel obstructions due to adhesion secondary to appendectomy. However, after the
appropriate work-up, it was determined that the obstruction was caused by angioedema of the small bowel. The patient was treated with C1 esterase inhibitors, and
after 24h, a repeat abdominal and pelvic CT showed complete resolution of the
obstruction and free uid levels. Following successful treatment, the patient admitted to a history of previous episodes of similar but mild abdominal pain that resolved
without intervention. During his gastroenterology follow-up appointment, the
patient underwent an esophagogastroduodenoscopy and a colonoscopy to rule out
other conditions such as Crohn’s disease or malignancy and was found to have
chronic gastritis. He also followed up with an immunologist for further management of his HAE.His nal diagnosis was small bowel obstruction due to HAE and
chronic gastritis.
Differential Diagnosis
1. Acute pancreatitis– The patient presented with a 2-day history of progressively
worsening abdominal pain as well as nausea and vomiting.
2. Acute cholecystitis – The patient presented with RUQ, epigastric, and central
abdominal pain as well as nausea and vomiting.
3. Small bowel obstruction– Secondary to adhesions from a previous appendec-
tomy, decreased bowel sounds.
14
4. Ischemic bowel– A 2-day history of abdominal pain with decreased bowel sounds.
5. Diverticulosis– A history of abdominal pain, nausea, vomiting, abdominal dis-
tension, and constipation.
6. Renal colic– Right-sided abdominal pain with episodes of nausea and vomiting.
7. Gastritis– The patient presented with a 2-day history of progressively worsening
abdominal pain as well as nausea and vomiting.
8. Crohn’s disease – A history of abdominal pain, nausea, vomiting, and
constipation.
A. Khorochkov
What WasMisdiagnosed inThis Case andWhy?
This case was misdiagnosed due to the symptomatically nonspecic disease presentation and the lack of physician familiarity with hereditary angioedema.
Discussion
In the case, a 52-year-old man presented with a 2-day history of right upper quadrant pain combined with episodes of nausea and vomiting. Despite the patient’s
known history of HAE, the initial differentials included acute pancreatitis and
acute cholecystitis due to the location of the pain. Bowel obstruction due to adhesions from an appendectomy was also considered. After further investigation, it
was eventually determined to be intestinal obstruction secondary to HAE and
treated with C1 esterase inhibitors, resulting in a full recovery. Even with the
patient’s history, obstruction secondary to HAE was not considered a differential
until further investigation, thus delaying appropriate treatment [1]. Inherited
HAE is subdivided into a deciency (type 1), in which there are low levels of
C1-INH, or a defect (type 2), which has nonfunctional but normal levels of
C1-INH [2, 11]. Both variants will have a depletion of complement 2 (C2) and
complement 4 (C4) proteins since they are consumed by the uninhibited action of
C1 and can serve as an excellent initial diagnostic indicator of HAE [8, 11, 12,
14–18]. Other less common variants of HAE can have both normal function and
amount of C1-INH [1, 11]. These types involve mutations of Factor XII, kininogen-1, or can even be unknown, but ultimately will lead to the unchecked generation of bradykinin [1].
Under normal conditions, the classical complement cascade begins with C1 activation via antigen-antibody complexes. In turn, C1 will activate subsequent complement signals until, ultimately, the membrane attack complex is formed. C1-INH
also suppresses FXII and Kallikrein and is involved in other processes. Thus, the
2 Angioedema Bowel Blockade: The Misdiagnosis of Hereditary Angioedema as…
15
lack of inhibitor leads to uncontrolled activation of FXIIa and kallikrein, which
results in increased bradykinin production [7, 12]. This vasodilatory peptide can
increase pain and relaxes the vascular smooth muscles, causing increased capillary
permeability [7, 12].
Uninhibited bradykinin release manifests as angioedema and can involve upper
and lower extremities, the face, trunk, and genitalia [19, 20]. Furthermore, angioedema can involve submucosal tissue such as the respiratory and gastrointestinal
tracts [3]. The angioedema of HAE can present in many ways leading to a differing
array of symptoms. This presentation makes it challenging to identify and may
require physicians to pay close attention to the patient’s medical history for episodes of unexplained abdominal pain since it is one of the most common presenting
symptoms [11]. Depending on the location, the abdominal symptoms can be easily
misdiagnosed as more common gastrointestinal maladies (e.g., gastroenteritis,
appendicitis, cholecystitis, acute pancreatitis, diverticulosis, etc.) [3, 9]. This misdi-
agnosis can lead to unnecessary procedures such as appendectomy, exploratory
laparotomy, and even hysterectomy [2, 4]. Swelling of subcutaneous tissue may
mimic the more common presentation of mast cell-induced allergic reactions (e.g.,
non-pruritic skin rash, urticaria, etc.) [14]. Other indicators to look out for are a history of endemic episodes of unknown cause or even inconclusive procedures [1,
11]. In addition, medications such as ACE inhibitors or oral contraceptives can
increase the overall levels of bradykinin and lead to increased frequency or increase
in the severity of angioedema attacks, so consideration should be taken when prescribing these [1, 15, 16]. It is essential to be aware of HAE as a possible differential
diagnosis since, if identied to be the cause, the treatment plan can focus on the
regulation of bradykinin and functional C1-INH levels to reduce the frequency and
severity of the angioedema episodes [1, 8, 19]. One quick identication method is
the Hereditary AngioEdema Rapid Triage tool. Using this tool can help identify a
cause for recurrent idiopathic angioedema [3, 7]. During acute HAE episodes,
prompt and early treatment can decrease the subsequent duration and pain intensity
compared to delayed treatment [7]. Medications used for the acute episodes include
human-puried plasma-derived C1 inhibitors, kallikrein inhibitors (i.e., ecallantide), or bradykinin B2 receptor antagonists (i.e., icatibant) [3]. After the HAE exacerbation resolves, rst-line prophylaxis involves the administration of C1 inhibitors,
monoclonal antibodies against kallikrein that prevent its function (i.e., lanadelumab)
[21, 22]. Second-line treatment options include attenuated androgens (i.e., danazol)
or tranexamic acid [3, 12, 21–23]. Early diagnosis and treatment will signicantly
improve quality of life [1, 7]. and prevent the patient from being subjected to further
investigation [1, 8]. Following treatment of the acute episode and subsequent longterm prophylactic management of HAE, the prognosis is generally favorable [12]
Fig.2.1.
16
Fig. 2.1 A quick step-by-step method to assess a patient that arrives with angioedema of unknown
origin [3, 7]. HAE, hereditary angioedema; C1-INH, C1 inhibitor; FHx, family history; FXII,
Factor 12
A. Khorochkov
Conclusion
Due to the broad range of tissue that can be affected and its nonspecic presentation, hereditary angioedema can mimic a range of other conditions. Subcutaneous
presentation of angioedema can resemble a cutaneous allergic reaction. If the angioedema exacerbation occurs in the submucosa of the GI, it can present as any number
of diseases in that location. Although not as common as conditions (e.g., diverticulosis, cholecystitis), physicians should be aware of HAE as a differential for gastrointestinal symptoms, especially in situations where symptoms have no identiable
cause or when the patient has a history of previously diagnosed HAE.
References
1. Jamil B, Naeem MS, Anachebe T, Majeed MH. Hereditary angio-oedema as a rare cause
of small-bowel obstruction. BMJ Case Rep. 2019;12(10):e231186. Published 2019 Oct 25.
https://doi.org/10.1136/bcr- 2019- 231186.
2. Cao Y, Liu S, Zhi Y.Recurrent and acute abdominal pain as the main clinical manifestation
in patients with hereditary angioedema. Allergy Asthma Proc. 2021;42(2):131–5. https://doi.
org/10.2500/aap.2021.42.210001.
3. Mumneh N, Tick M, Borum M.Angioedema with severe acute abdominal pain: think of
hereditary angioedema. Clin Res Hepatol Gastroenterol. 2021;45(4):101702. https://doi.
org/10.1016/j.clinre.2021.101702.
4. Patel N, Suarez LD, Kapur S, Bielory L.Hereditary angioedema and gastrointestinal complications: an extensive review of the literature. Case Rep Immunol. 2015;2015:925861. https://
doi.org/10.1155/2015/925861.
5. Magerl M, Gothe H, Krupka S, Lachmann A, Ohlmeier CA.Germany-wide survey study on the
patient journey of patients with hereditary angioedema. Orphanet J Rare Dis. 2021;16(1):97].