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Intestinal perforation due to miliary tuberculosis in a patient with myasthenia gravis
  1. Ahmed Ashraf Morgan1,
  2. Adil Mahmood1,
  3. Georgina K Russell2 and
  4. Onn Min Kon1
  1. 1Respiratory Medicine, Imperial College Healthcare NHS Trust, London, UK
  2. 2Chest & Allergy Clinic, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
  1. Correspondence to Dr Ahmed Ashraf Morgan; ahmed.morgan{at}nhs.net

Abstract

A man in his early 70s presented to the emergency department with a fall, following a history of fatigue and malodorous urine. On presentation, he was feverish, tachycardic and confused and was treated for presumed urinary sepsis. A chest radiograph showed increased opacification in the left upper lobe with calcification. CT imaging and bronchoalveolar lavage demonstrated miliary tuberculosis infection. His background included myasthenia gravis, which led to challenges in selecting appropriate antituberculosis treatment. During his stay, he developed sudden-onset abdominal pain due to intestinal perforation. He subsequently deteriorated and underwent multiple interventions, including a Hartmann’s procedure and ileocaecal resection. Histological examination of his sigmoid colon revealed abundant acid-fast bacilli. Unfortunately, the patient died due to multiorgan failure in the context of several complications. This case highlights intestinal perforation as a rare complication of miliary tuberculosis and emphasises the importance of being vigilant for this potential complication.

  • Tuberculosis
  • TB and other respiratory infections
  • Gastrointestinal surgery
  • Unwanted effects / adverse reactions
  • Neuromuscular disease

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Background

Tuberculosis (TB) is an ongoing global public health problem that affected around 10 million people worldwide in 2019.1 Of all infectious diseases, it is a foremost and ongoing cause of death, costing an estimated 1.4 million lives in the aforementioned year.1 In the UK, there was an incidence of 8.4 per 100 000 in 2019.2 As per the WHO standards, the UK is classed as a low incidence country.1 2

We report a case of miliary TB complicated by intestinal perforation and a background of myasthenia gravis (MG), which necessitated medical, surgical and pharmaceutical collaboration. The case highlights the wide range of complications that can arise from TB and the importance of multidisciplinary teamwork in optimising patient care. It also demonstrates the complexity of managing TB in patients with comorbidities that can influence treatment decisions. In choosing the anti-TB drug regimen, consideration had to be made for MG and the impact each agent would have on the disease, with a fine balance between exacerbation of MG and adequate treatment of TB.

Case presentation

A man in his early 70s, with a previous medical history of MG (treated with prednisolone and pyridostigmine), osteoporosis and gout, presented to hospital with a fall. He reported increased fatigue, occasional dysphagia and foul-smelling urine over the last month but denied any shortness of breath or cough. He was born in Vietnam and had been living independently in the UK.

On examination, he was feverish, tachycardic with a heart rate of 104/min and confused. His blood pressure was 123/70 mm Hg. General examination demonstrated bilateral ptosis with weakness in all limbs concordant with MG, and on auscultation of his chest, there were few scattered crackles with normal heart sounds. An initial impression of urinary sepsis on a background of MG was made.

A chest radiograph identified increased opacification in the left upper lobe with areas of calcification. On further exploration, the patient revealed that his mother had TB when he was a child and that he had not received any treatment or prophylaxis for this. Further investigations confirmed miliary TB and treatment was commenced. A few days later, he was noted to have fresh blood mixed with his stool and subsequent abdominal pain, which complicated his inpatient admission.

Investigations

During his prolonged stay, the patient underwent numerous investigations. Following initial chest radiographic findings, high-resolution CT scan of the thorax demonstrated multiple soft tissue densities in the left upper lobe and widespread uniform pulmonary nodules across all lobes, consistent with miliary TB (figure 1). Bronchoalveolar lavage (BAL) fluid was sent for the Xpert MTB/RIF assay and was positive for Mycobacterium tuberculosis (MTB) complex DNA and was rifampicin resistance negative. BAL culture revealed scanty acid-fast bacilli (AFB) and was positive for MTB after 13 days, which was susceptible to all first-line medications. Cerebrospinal fluid (CSF) was negative for MTB complex DNA and a viral screen was also negative. MRI of the brain was performed due to initial patient confusion and this was discussed at the radiology multidisciplinary meeting. It displayed no evidence of TB meningitis and no leptomeningeal enhancement. Blood testing revealed that he was HIV negative, ruling this out as a potential cause of immunosuppression.

Figure 1

Axial maximum intensity projection (MIP) image of an unenhanced CT thorax. This more clearly demonstrates the innumerable tiny/miliary pulmonary nodules.

After a reported episode of acute abdominal pain, CT scan of the abdomen and pelvis identified free gas in the abdomen (figure 2). Initial laparotomy was performed, which showed sigmoid perforation. Later on, repeat CT scan of the abdomen and pelvis demonstrated diffuse mural oedema and hypoenhancement of a portion of proximal ileum, indicative of small bowel ischaemia. Repeat laparotomy was conducted, which showed dusky patches of jejunum and ascitic fluid. Following this, a further CT scan of the thorax, abdomen and pelvis revealed signs of profound hypoperfusion complex with diffuse small bowel and colonic submucosal oedema. Another laparotomy was conducted, identifying a small bowel perforation near to the ileocaecal valve and multiple granulomatous patches over the small bowel. He proceeded to have a series of CT scans, with a final CT scan of the abdomen and pelvis showing anastomotic breakdown and leakage of enteric contents through a dehisced midline laparotomy wound.

Figure 2

CT abdomen and pelvis showing perforation. (A) Axial image of a contrast-enhanced CT of the abdomen. This has been windowed to better appreciate the anti-dependent free extraluminal gas (red arrow). (B) Negative image of the same slice demonstrates the thin bowel wall (red arrow) with extraluminal gas (blue star).

Intestinal samples were taken for histology from two laparotomies. The first identified sigmoid ulceration and healing granulomatous inflammation as well as abundant AFB within the infiltrate (figure 3). An ileocaecal sample from the second laparotomy identified ischaemic ulceration and perforation of small bowel with lymph nodes replaced by hyalinising fibrosis and focal necrosis. A Ziehl-Neelsen stain showed scanty AFB.

Figure 3

Histology slides from sigmoid resection. (A) Partially healed granulomas and chronic inflammation with lymphocytes and histiocytes in area of ulceration. (B) A discrete epithelioid granuloma in adjacent large bowel. (C) Close up of granuloma with giant cells. (D) Ziehl-Neelsen stain showing acid-fast bacilli.

Differential diagnosis

On initial presentation, it was thought that the patient had sepsis secondary to a urinary tract infection. Following the left upper lobe infiltrate identified on chest radiograph and the high-resolution CT thorax findings, another possible diagnosis was miliary metastases with a primary upper lobe lung cancer. However, the uniform millet-sized nodules without a clear bronchial mass directed us closer to miliary TB and BAL fluid culture helped to confirm this. Adrenal TB was not a clinical concern, given stable observations and renal function.

Treatment

On admission, he was initially treated with broad-spectrum antibiotics for urinary sepsis. However, the management strategy rapidly adapted to the investigation findings and clinical progression of the patient.

Four days after admission, he was commenced on empiric treatment for TB: rifampicin 600 mg/day, isoniazid 300 mg/day, pyrazinamide 2 g/day and moxifloxacin 400 mg/day. His long-term prednisolone dose (15 mg/day) was also increased due to his acute illness and rifampicin initiation. Moxifloxacin was soon discontinued due to concerns regarding exacerbation of MG. In view of the biochemical abnormalities detected on his CSF (high protein of 81 mg/dL, low glucose of 2.4 mmol/L) and high disease burden, the aim was to continue anti-TB treatment for 9–12 months. Ethambutol initiation was initially delayed due to patient drowsiness and confusion, with difficulty in completing the necessary visual examination. However, due to worsening liver function tests, standard triple therapy was stopped, and the patient was started on linezolid 600 mg/day and ethambutol 1 g/day. Linezolid was used in place of amikacin in view of potential worsening of MG with aminoglycoside use. On improvement of his liver function, the regimen was transitioned to rifampicin 600 mg/day, isoniazid 300 mg/day, pyrazinamide 2 g/day, ethambutol 1 g/day and linezolid 600 mg/day.

Another key aspect of treatment was surgical intervention. Five days into his stay, he reported an episode of sudden-onset abdominal pain. Imaging showed free gas within the abdomen, and the surgical team carried out a laparotomy with Hartmann’s procedure for a sigmoid perforation and faecal peritonitis. Perioperative management was complicated by his previous medical history of MG, which required close consultation between the anaesthetic, neurology and pharmacy teams. Intravenous immunoglobulin was not started but prednisolone was switched to hydrocortisone. The patient was admitted to the intensive care unit (ICU) for postoperative management before being stepped down. Approximately 1 month following this, a diagnostic laparotomy was conducted due to concerns regarding increasing abdominal pain and ischaemic bowel on imaging. Dusky patches were identified over the jejunum, which improved with hot pack application. During this period, the patient was again managed in the ICU.

All TB treatment was held following the second laparotomy due to concerns regarding liver injury, severe thrombocytopenia and lactataemia. Isoniazid was first to be restarted in combination with meropenem and co-amoxiclav, and on discussion with the neurology team, it was agreed that moxifloxacin and amikacin could be started in view of infection severity. The resulting regimen was rifampicin 600 mg/day, isoniazid 300 mg/day, moxifloxacin 400 mg/day and amikacin 15 mg/kg/day.

Less than 2 weeks following the second operation, the patient underwent a relook laparotomy due to continued clinical deterioration and evidence of perforation. An ileocaecal and small bowel resection with terminal ileostomy-mucus fistula was performed. Ten days postprocedure, an active bleed was identified from a proximal branch of the superior mesenteric artery. The patient subsequently required insertion of an inferior vena cava filter as well as arterial embolisation.

Outcome and follow-up

Following the third laparotomy, there was anastomotic breakdown and dehiscence of the laparotomy wound. Unfortunately, the patient passed away 1 week after this—2 months after his admission to hospital. This was attributed to multiorgan failure in the context of large and small bowel perforation.

Discussion

The identification of new TB can prove challenging, especially in the elderly community. It has been found that those aged ≥65 years face a greater delay in initiation of treatment following symptom onset compared with those who are younger.3 Older patients are more likely to present with atypical and non-specific symptoms such as dyspnoea and lethargy, while the well-recognised features of TB such as night sweats and haemoptysis are more often seen in those who are younger. For this reason, it is important to keep TB in mind, particularly when radiological imaging is suggestive of infection, there is a family or social history of TB or the patient is from a country with high prevalence of infection.

There are numerous manifestations of TB, with extrapulmonary TB found in 59.9% of UK cases in 2019.2 Abdominal TB is one such manifestation and can involve the gastrointestinal tract, peritoneum or viscera. In particular, gastrointestinal TB predisposes to a multitude of complications, including perforation, abscess and obstruction.4 5 In 2019, 5.8% of new TB cases in the UK involved the gastrointestinal system and only 3.1% involved miliary TB.2 In our presented case, the patient had miliary TB with intestinal involvement. The literature demonstrates that the most common sites of gastrointestinal TB are the ileum and ileocaecal regions.5 6 Our patient had small bowel perforation near the ileocaecal valve, sigmoid perforation and multiple granulomatous lesions over the small intestine that were nearing perforation. This more disseminated picture likely reflects the haematogenous element rather than contiguous infection.

The literature suggests that intestinal tuberculosis results in perforation in 6.6%7–13%8 of cases. Perforation in the specific context of miliary TB is rarer, with few case reports and data suggesting it occurs in 0.1%9–1.9%10 of cases. Other case reports of intestinal perforation secondary to TB report a background of immunosuppression,11–13 which is concordant with our case. However, reports indicate that the mean age of patients with abdominal TB is around 30–40 years old,4 14 in contrast to our patient who was in his early 70s. Mortality in patients with abdominal TB has been reported to range from 1.4% to 20%.4 This increases with perforation and it is possible that the combination of factors such as age and immunosuppression contributed to the outcome in our case. Furthermore, earlier disease identification and effective TB treatment could improve prognosis.4

Contributing to the difficulty in identifying and managing abdominal TB is the wide variation in clinical presentation. It is a disease that can mimic the presentation of many other conditions. As with our case, the literature demonstrates that patients can report fever, lethargy and weight loss.4 6 11 Rectal bleeding has also been noted,11 as in this instance, although it is rare. The clinical picture can range from an acute abdomen requiring emergent surgical intervention to the identification of the disease as an incidental finding.11

There are various ways to establish a diagnosis of abdominal TB although low sensitivities can make it difficult. Ascitic fluid and biopsy showing MTB via culture or nucleic acid amplification test can confirm the diagnosis.4 14 It has been reported that the sensitivity of culture from intestinal biopsy is 50%, with AFB sensitivity at 38%.15 Sensitivity was found to be significantly higher when culture was combined with granulomatous pathology. The method of obtaining a sample for histology depends on the patient11; in our case, a laparotomy was the most appropriate given the acute nature of the situation. Additionally, we had obtained a positive BAL fluid culture, which was later corroborated by the identification of intestinal granulomas and AFB.

The National Institute for Health and Care Excellence recommends treating active TB with 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol. This is then followed by 4 months of isoniazid and rifampicin.16 Due to the high disease burden in our case, the initial goal was to aim for prolonged treatment (9–12 months). There was a delicate balance between the side effects of TB medication and inadequate treatment of the life-threatening infection. This resulted in several medications being held intermittently and reintroduced as per the patient’s blood test results and clinical status. An additional challenge was posed in the selection of treatment given the patient’s background history of MG, where much of the regimen with lower hepatotoxicity is contraindicated. For example, moxifloxacin can cause a life-threatening exacerbation of MG.17 This required liaison with the neurology team, and on discussion, the decision was made to prioritise treatment of TB at the risk of worsening MG. Pharmacist involvement was also vital throughout admission; however, there was no clear answer as to what the optimal regimen was, and the treatment had to be adapted to the evolving clinical picture.

The need for surgical intervention in certain patients with abdominal TB is vital; for example, those presenting with intestinal perforation.11 18 The choice of intervention and need for resection will depend on the extent of disease and patient status. Preoperative management in this case posed a greater challenge due to the patient’s background of MG. With each laparotomy, it was also made apparent that the risk of death had increased in light of the patient’s poor clinical condition and comorbidities. Known complications of surgical intervention include anastomotic leak and dehiscence,11 18 as unfortunately occurred in this case. Successive perforations led to multiple procedures, which resulted in a myriad of complications.

Multiple teams were involved in the care of our patient. This included TB specialist physicians, general surgeons, vascular surgeons, interventional radiologists, neurologists, haematologists, pharmacists and the intensive care team. This case demonstrates the importance of multidisciplinary teamwork and highlights the difficulties, which may arise when treating patients with complex presentations.

Patient’s perspective

Comments from the patient's brother: 'I really appreciate everyone trying to help my brother. He was afraid of going to hospital because he was concerned about the coronavirus and not having any visitors. It was difficult, especially in the beginning as he felt lonely, and I could not see him. However, he would have died in his bed if I did not take him to hospital. The time we are in made it harder. A lot of teams were involved in his case, and I appreciate what they did'.

Learning points

  • Miliary tuberculosis (TB) can involve the bowel and cause perforation.

  • Acute abdominal pain in a patient with TB should raise the thought of abdominal TB and its potential complications. A high degree of suspicion is required, especially in the context of immunosuppression.

  • Abdominal TB can be difficult to detect due to the wide variation in presentation and low sensitivity of many investigations. A combination of approaches is beneficial in confirming the diagnosis, such as intestinal biopsy with culture and tissue identification of granulomas.

  • Effective treatment of TB is key in avoiding complications, and it is important to assess the risks and benefits in patients with contraindications to treatment.

Ethics statements

Patient consent for publication

Acknowledgments

With thanks to Dr Samir Mahboobani (Cardiothoracic Radiology Consultant) for the images in ‘figure 1’ and ‘figure 2’. With thanks to Dr Priscilla Anketell (Pathology Consultant) for the images in ‘figure 3’.

References

Footnotes

  • Contributors The care of the patient and selection for the case report was led by GKR and OMK. All authors were involved in care during the patient’s hospital admission. All authors were also involved in writing of the report, with the initial draft written by AAM and revised by AM with further input and revision from GKR and OMK. Images were identified by GKR and OMK and supplied by the relevant clinicians.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.