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296
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Discussion

Tuberculosis of the lungs is prevalent worldwide, especially in developing coun­tries. Disseminated tuberculosis (TB) is an infection in two or more noncontiguous locations caused by Mycobacterium tuberculosis hematogenous dissemination due to primary infection or reactivation of a latent infection. Miliary tuberculosis also refers to TB that is progressing and widespread. Even if the conventional pathologic or radiologic signs are lacking, it implies a hematogenous spread to numerous organs [8, 9]. Tuberculosis is caused by the small aerobic non-motile bacillus Mycobacterium tuberculosis infecting the lungs (MTB). When patients with an active MTB infection cough, sneeze, or otherwise transmit their saliva, it spreads. Lung cancer is an etiologically complicated disease in which several genes play a role in the pathogenesis of the disease through various routes. Individuals may develop lung cancer when these genes interact with environmental conditions [7]. Tuberculosis must be distinguished from lung cancer to receive proper and timely treatment [10]. According to reports, delaying the identication and treatment of lung cancer often results in a poor outcome and survival rate [7]. However, because lung cancer and tuberculosis are often confused, an invasive biopsy separates the two diseases. Even radiologists with decades of expertise may misdiagnose tuber­culosis and lung cancer utilizing CT imaging data in clinical practice or even miss the diagnosis entirely [11]. Pulmonary nodules are spherical intrapulmonary lesions less than 3cm [12]. In both lung metastases and HDTB, several tiny pulmonary nodules are common. Because the imaging manifestations are so similar, it’s chal­lenging to make a denitive diagnosis [13]. Lung cancer nodules have dened edges and may contain cavities or ground-glass opacity. In hematogenous disseminated tuberculosis, the margins of nodules are not apparent and may show hollow or ground-glass opacity. The CT scan of the patient’s lungs revealed several spherical nodules of various sizes with distinct borders and partial fusion. The intrahepatic bile duct and pancreas were dilated, the pancreatic head was enlarged, and the spleen had several low-density foci. CA19-9 is regarded as a pancreatic cancer marker. Pancreatic and biliary ductal cells and stomach, colon, endometrial, and salivary epithelia produce CA19-9 [14]. CA19-9 is only seen in trace amounts in serum. On the other hand, this signal has low specicity [15]. CA19-9 overexpres­sion has been seen in various benign gastrointestinal illnesses and pancreatic tuber­culosis [16, 17]. CA19-9 levels were dramatically elevated in our patient, who also played a role in the misdiagnosis of the disease. Disseminated tuberculosis, once almost exclusively diagnosed in children or people with immunosuppression, is increasingly detected in adults with no apparent immunological deciency [18, 19]. The majority of these patients come from countries where tuberculosis is prevalent. Patients’ access to the healthcare system is hampered by several circumstances, including a language barrier and frequent relocation, which can lead to a delay in diagnosis and, as a result, disease progression [19, 20].
41 Hematogenous Disseminated Tuberculosis Misdiagnosed asMetastatic Lung Cancer
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Patients with disseminated TB and unusual radiographic ndings might undergo various diagnostic tests. Sputum that has been expectorated or induced should be sent for testing to conrm the diagnosis in these patients. The samples must be subjected to smear, PCR, and mycobacterial culture tests and these must be per­formed on two sputum samples for a denitive diagnosis. At least 5000–10,000 bacilli/mm specimens are required for a positive AFB sputum test, while M. tuber- culosis culture requires 10–100 microorganisms/mm [21, 22]. Endotracheal secre- tions and gastric lavage can also be utilized to establish the diagnosis if the patient cannot cough, as is often the case with comatose patients or children [23]. Fiber­optic bronchoscopy can provide alternative respiratory specimens for diagnosis in patients with suspected disseminated TB who have smear-negative or PCR­negative sputum or nonproductive cough or who are unable to expectorate through procedures such as bronchoalveolar lavage, bronchoscopic aspirate (BA), brush­ings, washings, and transbronchial biopsy (TBB) [24–26]. Specimens should be collected from as many locations as feasible to increase the chances of conrming the diagnosis. Furthermore, the utility of PET-CT in assessing the efcacy of TB treatment, particularly extrapulmonary TB, has long been acknowledged [27]. Unfortunately, due to its exorbitant cost, it is unavailable in China. For this reason, the patient also refused a PET-CT re-examination. Finally, a lung puncture biopsy revealed pulmonary tuberculosis. The “four-drug regimen,” consisting of two phases of rifampicin, isoniazid (INH), pyrazinamide, and ethambutol/streptomy­cin administered daily for the rst 2 months, is used to treat disseminated TB.Rifampicin and isoniazid are subsequently given for another 4 months, pos­sibly being prolonged to 7 months [28]. The anti-TB regimen cured our patient completely.

Conclusion

A greater understanding of hematogenous disseminated tuberculosis and its accom­panying characteristics could help a clinician’s index of suspicion and lead to a more accurate diagnosis. Patients with immunosuppression and in endemic areas present with persistent pyrexia of unexplained origin, weight loss, lassitude, hepa­tomegaly, splenomegaly, liver function abnormalities, and abnormal hematological signs; hematogenous disseminated tuberculosis should be suspected and targeted for quick diagnosis and treatment [27]. It can be challenging to distinguish lung TB from neoplasm based on clinical and radiographic symptoms. On 18-FDG-PET scans, both disorders show parenchymal inltrates with high metabolic activity and often have comparable symptoms. Considering tuberculosis as a differential diag­nosis for PET-positive lung inltrates might help prevent unnecessary diagnostic procedures, reducing diagnostic workup problems and expenses [1].
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References

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org/10.1016/S0140- 6736(05)67862- 2.
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9. Salvado G, Santos C, André M, Gomes C, Diogo N, Marques M, etal. Miliary tuberculosis. Rev Port Pneumol. 2002;8:315–27.
10. Patil S, Jadhav A.Short course of high-dose steroids for anaphylaxis caused are up of tuber­culosis: a case report. J Transl Int Med. 2019;7:39–42.
11. Cui EN, Yu T, Shang SJ, Wang XY, Jin YL, Dong Y, Zhao H, Luo YH, Jiang XR.Radiomics model for distinguishing tuberculosis and lung cancer on computed tomography scans. World J Clin Cases. 2020 Nov 6;8(21):5203–12. https://doi.org/10.12998/wjcc.v8.i21.5203.
12. Setio AAA, Traverso A, de Bel T, Berens MSN, Bogaard CVD, Cerello P, Chen H, Dou Q, Fantacci ME, Geurts B, Gugten RV, Heng PA, Jansen B, de Kaste MMJ, Kotov V, Lin JY, Manders JTMC, Sóñora-Mengana A, García-Naranjo JC, Papavasileiou E, Prokop M, Saletta M, Schaefer-Prokop CM, Scholten ET, Scholten L, Snoeren MM, Torres EL, Vandemeulebroucke J, Walasek N, Zuidhof GCA, Ginneken BV, Jacobs C.Validation, com­parison, and combination of algorithms for automatic detection of pulmonary nodules in com­puted tomography images: the LUNA16 challenge. Med Image Anal. 2017;42:1–13. https://
doi.org/10.1016/j.media.2017.06.015. Epub 2017 Jul 13
13. Onuigbo WI. Some nineteenth century ideas on links between tuberculous and can­cerous diseases of the lung. Br J Dis Chest. 1975 Jul;69:207–10. https://doi.
org/10.1016/0007- 0971(75)90081- 9.
14. Scarà S, Bottoni P, Scatena R.CA 19-9: biochemical and clinical aspects. Adv Exp Med Biol. 2015;867:247–60. https://doi.org/10.1007/978- 94- 017- 7215- 0_15.
15. Pavai S, Yap SF.The clinical signicance of elevated levels of serum CA 19-9. Med J Malaysia. 2003 Dec;58(5):667–72.
16. Bhatia V, Garg PK, Arora VK, Sharma R.Isolated pancreatic tuberculosis mimicking intra­ductal pancreatic mucinous tumor. Gastrointest Endosc. 2008;68(3):610–1. https://doi.
org/10.1016/j.gie.2007.12.022. Epub 2008 Mar 24
17. Yang YJ, Li YX, Liu XQ, Yang M, Liu K. Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy: a case report. World J Clin Cases. 2014 May 16;2(5):167–9. https://doi.org/10.12998/wjcc.v2.i5.167.
18. Odone A, Tillmann T, Sandgren A, Williams G, Rechel B, Ingleby D, Noori T, Mladovsky P, McKee M.Tuberculosis among migrant populations in the European Union and the European economic area. Eur J Pub Health. 2015;25(3):506–12. https://doi.org/10.1093/eurpub/cku208. Epub 2014 Dec 13
41 Hematogenous Disseminated Tuberculosis Misdiagnosed asMetastatic Lung Cancer
19. Suarez I, Maria Funger S, Jung N, etal. Severe disseminated tuberculosis in HIV-negative refugees. Lancet Infect Dis. 2019; pii: 1473–3099;19:30162–8.
20. European Centre for Disease Prevention and Control. Migrant health: background note to the ‘ECDC Report on migration and infectious diseases in the EU’. European Centre for disease prevention and control. 2009.
21. Mert A, Bilir M, Tabak F, Ozaras R, Ozturk R, Senturk H, etal. Miliary tuberculosis: clinical manifestations, diagnosis and outcome in 38 adults. Respirology. 2001;6:217–24.
22. Wang JY, Hsueh PR, Wang SK, Jan IS, Lee LN, Liaw YS, etal. Disseminated tuberculosis: a 10-year experience in a medical center. Medicine (Baltimore). 2007;86:39–46.
23. Grace M, Shameer VK, Bharathan R, Chandrikakumari K.Disseminated tuberculosis present­ing as acute lung injury. J Assoc Chest Physicians. 2014;2:68–70.
24. Tamura A, Shimada M, Matsui Y, Kawashima M, Suzuki J, Ariga H, et al. The value of beroptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre­bronchoscopic sputum specimens were negative both for smear and PCR analyses. Intern Med. 2010;49:95–102.
25. Chen NH, Liu YC, Tsao TC, Wu TL, Hsieh MJ, Chuang ML, etal. Combined bronchoalveolar lavage and polymerase chain reaction in the diagnosis of pulmonary tuberculosis in smear­negative patients. Int J Tuberc Lung Dis. 2002;6:350–5.
26. Jacomelli M, Silva PR, Rodrigues AJ, Demarzo SE, Seicento M, Figueiredo VR, et al. Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results. J Bras Pneumol. 2012;38:167–73.
27. Yates JA, Collis OA, Sueblinvong T, Collis TK.Red snappers and red herrings: pelvic tuber­culosis causing elevated CA 125 and mimicking advanced ovarian cancer. A case report and literature review. Hawaii J med. Public Health. 2017 Aug;76(8):220–4.
28. Khan FY. Review of literature on disseminated tuberculosis with emphasis on the focused diagnostic workup. J Family Community Med. 2019 May-Aug;26(2):83–91. https://doi.
org/10.4103/jfcm.JFCM_106_18.
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Chapter 42
Severe Abdominal Sepsis Misdiagnosed asPelvic Inammatory Disease
SrushtiShahi
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Describe the pathophysiology of pelvic inammatory disease.
2. Enumerate the signs and symptoms of pelvic inammatory disease.
3. Recognize the diagnostic criteria used to diagnose pelvic inammatory disease.
4. List the CDC-recommended pelvic inammatory disease treatment regimens.
5. Consider all essential information of the medical history and the physical exami­nation of patients who present with symptomatology suspecting pelvic inam­matory disease to make an appropriate differential diagnosis.
6. Describe ways for enhancing care coordination and outcomes in patients with pelvic inammatory disease using an interprofessional team.
7. Explain why asymptomatic women should be screened and treated.

Introduction

Sexually transmitted diseases (STDs) continue to take a heavy toll on our nation’s health. ~Ronald Valdiserri
Pelvic inammatory disease is an infection most commonly caused by Neisseria gonorrhoeae and Chlamydia trachomatis. It is an upper genital tract polymicrobial infection [1]. PID affects the uterus, ovaries, fallopian tubes, and cervix, which are all organs of the female reproductive system [2, 3]. There are 750,000 cases of PID
S. Shahi (*) St. Martinus University Faculty of Medicine, Willemstad, Curacao e-mail: srushti.shahi@martinus.edu
© 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_42
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S. Shahi
each year in the United States, mainly in women 15 to 29years of age. The sort key recommendation from the AAFP states that screening for lower genital tract chla­mydial infection in younger and high-risk populations is recommended to reduce PID incidence [4–6]. Asymptomatic disease should be treated. PID can be fatal if not treated at the appropriate time or left untreated or undiagnosed. Fertility may be impacted by PID.According to studies, one in eight PID patients experienced trou­ble getting pregnant. Recurring infections made it more difcult for people to become pregnant. A fertilized egg must go from your ovary down your fallopian tube and into your uterus (womb). It can then be fertilized by the sperm. However, PID-related bacteria might leave your fallopian tubes scarred. The egg has a greater difculty traveling where it needs to go because of the scar tissue [7–9]. In women, sexually transmitted diseases (STDs) that go untreated can lead to pelvic inamma­tory disease (PID), a dangerous disorder. One in every eight women with a history of PID has trouble conceiving [4–6, 10, 11]. Its diagnosis is made clinically with a history of present illness and past medical history, most likely presented as lower abdominal pain, cervical motion tenderness, abnormal bleeding, dyspareunia, men­orrhagia, metrorrhagia, fever, nausea, and vomiting, and is one of the most common causes of infertility after uterine broids and polyps [10, 12]. Salpingitis can be diagnosed more accurately with laparoscopy, as well a more complete bacteriologic diagnosis. However, this diagnostic tool is frequently unavailable, and its usage is difcult to justify when symptoms are minor or ambiguous. Furthermore, laparos­copy will not detect endometritis and may miss minor fallopian tube irritation. Whether or not the woman ts any of the following factors will determine whether or not hospitalization is necessary: [13, 14].
• One cannot exclude surgical emergencies (like appendicitis).
• Obstructive ovarian cyst.
• Pregnancy.
• Severe illness, nausea, or a temperature of more than 38.5°C (101°F).
• Incapable of adhering to or sustaining an outpatient oral regimen.
• No clinical benet from oral antibiotic treatment.
As a result, a PID diagnosis is frequently based on ambiguous clinical ndings [7, 14–16]. When compared to laparoscopy, data show that a clinical diagnosis of symptomatic PID has a positive predictive value of 65–90% for salpingitis [8, 9, 14,
17–23]. The positive predictive value of a clinical diagnosis of acute PID is deter-
mined by the epidemiologic characteristics of the population, with higher positive predictive values among sexually active young women (especially adolescents), women who visit STD clinics, and those who live in areas where gonorrhea or chla­mydia is common [24]. A single historical, physical, or laboratory nding is neither sensitive nor specic for the diagnosis of acute PID, regardless of its positive pre­dictive value. Endometrial biopsy with histopathologic evidence of endometritis; transvaginal sonography or magnetic resonance imaging techniques showing thick­ened, uid-lled tubes with or without free pelvic uid or tubo-ovarian complex, or Doppler studies indicating pelvic infection (e.g., tubal hyperemia); and laparoscopic ndings consistent with PID are more specic criteria for diagnosing PID [7, 12,
42 Severe Abdominal Sepsis Misdiagnosed asPelvic Inammatory Disease
303
25]. In some circumstances, a diagnostic evaluation that involves some of these
more elaborate procedures may be necessary. The clinical response to outpatient treatment is comparable in younger and older women, and there is no evidence to suggest that adolescents have better outcomes from hospitalization for PID treat­ment [22]; because endometritis is the only symptom of PID in some women, endo­metrial biopsy is recommended for women having laparoscopy who do not have visual evidence of salpingitis [2]. It may also be confused with symptoms of appen­dicitis and ectopic pregnancy. Empiric, broad-spectrum coverage of probable infec­tions should be included in PID therapy regimens. In randomized clinical trials with short-term follow-up, multiple parenteral and oral antibiotic regimens were effec­tive in attaining clinical and microbiologic cures. Because early administration of prescribed antimicrobials is required to prevent long-term effects, treatment should begin as soon as the presumptive diagnosis is made [5, 8, 9]. Parenteral and oral regimens appear to be equally effective for women with mild-to-moderate clinical severity of PID.Doxycycline should, whenever possible, be given orally due to the discomfort associated with IV infusion. The bioavailability of metronidazole and doxycycline following oral and intravenous treatment is equivalent. When possible, ladies without a serious sickness or tubo-ovarian abscess should try taking metroni­dazole orally rather than intravenously because it is well absorbed. It is advised to switch to oral medication with doxycycline 100mg twice daily and metronidazole 500mg twice daily to nish the necessary 14days of antimicrobial therapy after treatment response with parenteral therapy [2, 4–6, 10–12, 15, 26]. Women with mild-to-moderate acute PID may be candidates for IM or oral therapy because the clinical results of these regimens are comparable to those of IV therapy [12, 15, 24]. Within 72h, women who do not react to IM or oral medication should be reevalu­ated to conrm the diagnosis and given IV therapy. First-generation cephalosporins carry the greatest risk of penicillin cross-reactivity, although the risk is minimal for most second-generation (like cefoxitin) and all third-generation (like ceftriaxone) cephalosporins. To prevent disease transmission, women should be told to refrain from sexual activity until their treatment is nished, their symptoms have subsided, and their sex partners have been treated (Chlamydial Infections; Gonococcal
Infections) [3, 17, 26, 27]. All women diagnosed with PID should have gonorrhea, chlamydia, HIV, and syphilis tested. The utility of testing for M. genitalium in
women with PID is uncertain (Mycoplasma genitalium) [21, 24, 28]. During ther­apy, all forms of contraception can be used. Maternal morbidity and premature birth are serious risks for pregnant women suspected of having PID.With the advice of an expert in infectious diseases, these ladies should be admitted to the hospital and given IV antibiotics [19, 22, 29]. Additional advice on taking care of yourself is as follows:
• To avoid transferring bacteria from your vagina into your uterus and fallopian
tubes, avoid douching.
• After taking the medication for a few days, visit your doctor again to determine
how well it is working.
• As directed, take all of your medications.
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S. Shahi
• To avoid infections, use dental dams or condoms each time you have sex.
• Wait a week after nishing your medication—and your partner’s—before start-
ing up again with your sexual relationship.
Below is a case misdiagnosed as PID due to elevated markers, imaging, and his­tory [20, 29].

Clinical Case Presentation

A 41-year-old Caucasian woman was hospitalized in the hospital’s intensive care unit with severe diabetic ketoacidosis. The patient had been sick and vomiting the day before admission and was eventually found unconscious and admitted to the hospital. Wild type 1 diabetes on insulin, diabetic retinopathy, depression, anxiety, and latent hepatitis C were all present in the patient’s medical history. She had been an intravenous drug user in the past, was on buprenorphine treatment with occa­sional benzodiazepine and opioid addiction, and smoked cigarettes. Her surgical procedures were laparoscopic bilateral tubal ligation and a large loop excision of the transformation zone (LLETZ) conization for a CIN 2 cervical lesion. Her tempera­ture was 29.4°C, her respiration rate was 28, her pulse was 75, her blood pressure was 135/87mmHg, and her Glasgow Coma Scale (GCS) was 10 when she was admitted. Severe metabolic acidosis, acute renal failure, and inammation were dis­covered in laboratory tests. Given her highly elevated inammatory markers and an unknown infection focus, the patient was started on therapy according to hospital diabetic ketoacidosis (DKA) protocol and intravenous meropenem. When the patient’s condition had stabilized, she was discharged to the medical ward. She felt feverish a few days later and began complaining of lower abdomen pain, nausea, and vaginal bleeding during her period. Inammatory markers were found to be increasing. The surgical team examined her and discovered she was constipated, so she was given laxatives. To pinpoint the infection’s source, a pelvic scan was sched­uled. Figure42.1 shows the complex uid within the pouch of Douglas. According to this research, pelvic infection is the most likely cause. The gynecology team evaluated the patient, and oral co-amoxicillin was prescribed.
On this medication, inammatory indicators that had begun to decline on meropenem began to climb. As a result, the antibiotics were changed to oral cip­rooxacin and metronidazole. The woman complained of nausea, a metronidazole adverse effect throughout her hospital stay. When the patient was afebrile and feeling better, she was sent home with oral antibiotics. The patient returned to our hospital’s emergency department 3weeks later, complaining primarily of right iliac fossa pain, nausea, and anorexia. A hyperechogenic mass was observed in the pouch of Douglas on a transvaginal bedside ultrasound scan (Fig.42.2) which was interpreted as an adnexal mass given the previous diagnosis of pelvic inamma­tory disease (PID). Due to the patient’s pain, the scan had to be stopped. An
42 Severe Abdominal Sepsis Misdiagnosed asPelvic Inammatory Disease
Fig. 42.1 Complex free uid. Source: www.hindawi.com/journals/cris/2018/9561798/
305
Fig. 42.2 Mass in the pouch of Douglas. Source: www.hindawi.com/journals/cris/2018/9561798/
abdominal (CT) computed tomography scan was scheduled to analyze the tumor further.
The transvaginal images were discussed with radiological colleagues but could not be linked to the CT ndings (Fig.42.3), which described the pelvic appear­ances as generic. Some pockets of uid and enlarged loops of the small bowel
306
Fig. 42.3 CT scan with nonspecic inammatory changes. Source: www.hindawi.com/journals/
cris/2018/9561798/
S. Shahi
indicate that the small bowel was involved in a secondary inammatory process in the pelvis. The surgical team re-examined the patient, who advised that a surgical etiology for the patient’s symptoms was doubtful. The gynecological group planned a diagnostic laparoscopy with the surgical team on standby. The patient began vomiting heavily while awaiting the procedure, necessitating the insertion of a nasogastric tube. Internal genitalia were found to be expected after diagnostic lapa­roscopy. The operation was changed to a midline laparotomy after the surgical team identied adherent intestinal tissue. In the upper region of the pelvis, there was a complicated, inammatory mass with an abscess cavity. The ileum was fully gangrenous and necrotic but structurally intact in a 10 to 15cm length. Surprisingly, there was no small bowel blockage, and the contents of the small bowel appeared to be moving through the gangrenous ileum’s lumen. The presence of an expanded node in the ileal mesentery, along with signicant brosis, raised the possibility of a neuroendocrine tumor (NET) nodal metastasis causing a mesenteric vascular blockage. A double-barrelled stoma was made after the inammatory mass was excised, and an ileocolic resection was performed. The patient fully recovered fol­lowing the surgery and was sent home a week later. The histology report revealed the presence of a well-differentiated ileal neuroendocrine primary tumor, which was not visible on laparotomy. One of the 20 mesenteric lymph nodes in the resected material was metastatic. When the CT imaging was reviewed after sur­gery, neither the primary tumor nor the nodal mass could be distinguished from the inammatory tissue. A multidisciplinary tumor meeting was held for the patient,