Complexities in pediatric tuberculosis: a case of advanced disease complicated by deep vein thrombosis and enterocutaneous fistula from Ethiopia

Abstract

Tuberculosis (TB) remains a leading global infectious disease, causing nearly 4,000 deaths daily, particularly affecting children under five. This case illustrates the complexities of diagnosing and treating advanced tuberculosis complications in a 6-year-old child who presented with deep vein thrombosis (DVT), an enterocutaneous fistula, and malnourishment. Causality was called into question by the connection between these conditions. Antibiotics, anticoagulants, antituberculosis drugs, fresh frozen plasma, stoma bag wound care, and nutritional support were all part of the patient’s treatment. She was discharged from the hospital with improvement after 15 days. The complex relationships among venous thromboembolism, malnourishment, and chronic infection are highlighted in this instance, underscoring the necessity of timely and thorough management of advanced TB to address the nutritional and infectious components of the patient’s condition.

Introduction

Mycobacterium tuberculosis has been a significant infectious disease for nearly 4,000 years, with the World Health Organization (WHO) estimating that about 95% of tuberculosis (TB) cases occur in impoverished regions [1, 2]. Ethiopia, which has an incidence rate of 140 per 100,000 people (157,000 cases yearly), is one of the 30 nations with the highest TB burden, accounting for 87% of new cases in 2019. Just 41% of TB cases that were reported in 2020 had bacteriological confirmation; the other cases were either extrapulmonary or clinically diagnosed [1–3]. Because of nonspecific symptoms, diagnosing tuberculosis in children is extremely difficult, and children under five years of age are more likely to develop serious illness. Although uncommon, tuberculous peritonitis mostly affects young boys and can result from bacilli ingestion or hematogenous spread [1, 4].

Extrapulmonary manifestations of TB, such as tuberculous enteritis, account for 30–40% of cases and can lead to complications such as enterocutaneous fistulas, which are uncommon and usually occur post-surgery [5]. Weight loss, fever, and stomach pain are signs of intestinal TB, with the ileocecal region particularly impacted by enlarged lymphoid tissue [6, 7]. Intestinal obstruction and perforation are possible complications; enterocutaneous fistulas are an uncommon manifestation [6]. Thromboembolic events (TEs), which can have a major influence on morbidity, are another issue that pediatric tertiary care centers must deal with. Compared with the general pediatric population, hospitalized children have a much greater incidence of venous thromboembolism (VTE), which is frequently associated with procedures such as central venous catheterization [1, 8]. It is unusual to appear in children when they have diseases such as Mycobacterium TB [9]. Reduced antithrombin III, elevated plasma fibrinogen and factor VIII levels, and reactive thrombocytosis are the mechanisms that cause deep venous thrombosis in tuberculosis [8, 9].

This report presents the case of a 6-year-old child with bacteriologically confirmed widespread tuberculosis, severe acute malnutrition, deep vein thrombosis (DVT), and a spontaneous enterocutaneous fistula. This case appears to be one of the few documented instances of this combination of rare TB complications successfully treated, highlighting the complexities involved in managing such multifaceted pediatric cases.

Case report

A 6-year-old girl was referred to our hospital with severe acute malnutrition, an abdominal mass, and an enterocutaneous fistula. Despite the initial treatment, her condition worsened over three months, marked by significant weight loss, night sweats, appetite loss, worsening nocturnal cough, and extensive swelling that started in her feet and progressed to her entire body. In the past week, she experienced a foul-smelling discharge from her umbilicus resembling feces. Two neighbors were diagnosed with tuberculosis, one previously treated and declared cured, while the other was undergoing therapy. The girl is fully vaccinated, has no recent drug history or trauma, and is the third of five children in a farming family.

On examination, she appeared chronically ill with a respiratory rate of 24 breaths per minute, tachycardic (pulse rate = 134), afebrile (Temp = 36.5 °C), and oxygen saturation of 95%. She was 104 cm tall, weighed 13.9 kg (body mass index (BMI): 12.85 kg/m²), and had a blood pressure of 100/60 mmHg, indicating severe underweight and moderate acute wasting. Her hair was sparse; the sclera’s were non-icteric and pink. Examination revealed multiple matted, nontender cervical lymph nodes and submental region with the largest measuring 3 × 3 cm. Abdominal examination showed a ballottable organ in the right upper quadrant (RUQ) with positive signs of fluid collection, erythema around the umbilicus, and distension. The umbilicus discharged a dark greenish, foul-smelling fluid (Fig. 1). The perirectal examination revealed soft, well-formed feces, while the musculoskeletal assessment indicated bilateral Grade III pitting edema with shiny swelling and thigh tenderness. She was conscious and alert.

Fig. 1.

The child’s abdomen was photographed on the third day of admission, showing a protruded abdomen, everted umbilicus dry and vigorous seeping, as well as stool-tingled discharge on her clothing (green arrow) and umbilicus (blue arrow) through entero-cutaneous fistula

Investigations

Her results from the initial lab investigation included complete blood cell count, Leukocytosis (White blood cells, WBC = 16100/mm3 with lymphocyte predominance (77%). Her serum albumin level was low and urine analysis was unremarkable. Peritoneal fluid Gene Xpert Mycobacterium Tuberculosis and Rifampicin resistance (MTB/RIF) Assay detected MTB without resistance detected to first line anti-TB and cytology suggests lymphocytic effusion which is still on line of TB. Lower limbs and abdominal-pelvic post-contrast Computed Tomography (CT scan) results suggests disseminated TB to (Liver, Intestine, Peritoneum, Cutaneous) with ascites and there is an abnormal connection between the bowel and the overlying skin suggesting enterocutaneous fistula, with associated fluid collection in the surrounding soft tissues (Fig. 2), whereas Doppler ultrasound indicates bilateral proximal deep venous thrombosis (DVT), describing there is bilateral common femoral vein, proximal superficial femoral vein and left iliac color filling defect with subcutaneous edema (left > right). Mycobacterium tuberculosis was not found in the sputum or discharge via the fistula, and the erythrocyte sedimentation rate (ESR) was normal. No abnormality was found in the chest X-ray image and Fine Needle Aspiration Cytology (FNAC) results from sub-mental lymph nodes indicated granulomatous inflammation consistent with tuberculosis. All other baseline investigations, serum electrolytes, coagulation profile, and organ function tests were unremarkable.

Fig. 2.

Disseminated TB involving the lung, peritoneum, bowel, and intrabdominal lymph nodes (LAPs) (A) with associated enterocutanous fistula (B), ascites (C), and inferior vena cava (IVC) compression with retroperitoneal nodal masses that is causing acute DVT in the left lower extremity is shown by a post-IV contrast Thoraco-Abdominal-Pelvic CT scan

Management

Therefore, a diagnosis of edematous severe acute malnutrition and disseminated tuberculosis to (lung, liver, intestine, lymph nodes, peritoneum) with enterocutaneous fistula (ECF) and bilateral lower extremities proximal DVT was made, and she began intravenous ceftriaxone and metronidazole for a week, transfused fresh frozen plasma (FFP), nutritional management with formula F-75, F-100 and Ready to use therapeutic Feeding (RUTF) based on WHO protocol of malnutrition management, and intensive phase of anti-TB treatment with ethambutol, isoniazid, rifampicin, pyrazinamide based on her weight for 2 months followed by isoniazid and rifampicin for next 4 months with daily pyridoxine. She also started unfractionated heparin with oral warfarin overlapped for 5 days, then discontinued unfractionated heparin (UFH) when the International Normalized Ratio (INR) become 2.3 and A stoma bag was placed over the fistula site to collect the effluent and shield the surrounding skin with monitoring of fistula output and wound care daily.

Outcome

Subsequently, the child’s condition began to improve, as shown by normal vital signs, a decrease in weight and edema and an increase in appetite, a decrease in the shininess of the abdominal skin, distention with a decrease in abdominal girth measurement, reducing leg discomfort and swelling while bilateral range of motion is restored and a decrease in the amount of discharge through enterocutaneous fistula that gradually stopped within ten days of the start of treatment. She was discharged with a week appointment after 15 days of hospital stay. The child is currently in the follow-up clinic with no complaints after quitting all medications and completing six months of daily anti-tuberculosis treatment and daily warfarin. The patient’s weight initially decreased from 13.9 kg to 12.1 kg following nutritional rehabilitation, indicating improvement as demonstrated by the decrease in edema and a healthy appetite. At the final measurement, it gradually increased to 16.2 kg, yielding a BMI of 14.98 kg/m2, which is normal for her age and sex. With an emphasis on the deep and superficial veins as well as the continental veins, all follow-up physical examinations and tests were normal, including an abdominal ultrasound and Doppler ultrasound radiographic evaluations of the lower limb, were performed with no postphlebitic sequential lesions after 2 months and at the end of treatment.

Discussion

An enterocutaneous fistula is an abnormal connection between the skin and digestive tract, with 75%–85% being iatrogenic and the remainder associated with conditions like tuberculosis or Crohn’s disease [10, 11]. The mortality and morbidity rates are significant, estimated at 10–20%, due to complications such as sepsis and nutritional deficiencies [11, 12]. Enterocutaneous tuberculosis can arise from various mechanisms, including bowel disease spreading to adjacent structures or unnoticed intestinal damage [10].

Initial management involves correcting fluid and electrolyte imbalances, treating sepsis, controlling output, and providing wound care and psychological support [13, 14]. Treatment varies based on the output volume: low-output fistulas may be managed conservatively, while high-output cases often require surgical intervention for resection and anastomosis of the affected segment. However, conservative methods may not always achieve permanent closure, necessitating careful consideration of surgical options when needed [13, 15].

In our case, the patient with a low-output enterocutaneous fistula was effectively treated conservatively, showing improvement within 2 weeks. This aligns with ShahWani’s report of a patient who also benefited from conservative management involving antibiotics and intravenous fluids [15]. Taggarshe et al. found that conservative treatment was more effective for 34 of 45 low-output fistula patients over ten years [14]. Our management aligns with the case of Delta Iswara et al. of intestinal TB with enterocutaneous fistula, using a stoma bag, leading to significant symptom improvement and reduced output after two weeks [11]. Additionally, A. Josaphat et al. reported a similar case in a severely malnourished child, emphasizing the efficacy of conservative approaches [16].

Bilateral lower extremity DVT is rare in children, but factors such as prolonged immobility, hypercoagulable states due to malnutrition and infection, and genetic disorders can contribute to its occurrence [17, 18]. Low-molecular-weight heparin is the preferred treatment for pediatric DVT due to its efficacy and convenience, while vitamin K antagonists are generally not recommended for those under 12 months of age but can be used in older children [19, 20]. Anticoagulation is typically advised for three to six months, with extensions based on ongoing prothrombotic risk factors. In our case, the patient received unfractionated heparin (UFH) and warfarin for the first 5 days, followed by warfarin alone during anti-TB treatment. Close monitoring of INR was essential due to potential interactions between warfarin and TB medications; rifampicin may reduce the effectiveness of warfarin by inducing liver enzymes, while isoniazid can enhance its anticoagulant effect by inhibiting metabolism. Thus, it is crucial to adjust the warfarin dosage according to INR levels, lowering it if isoniazid raises the INR or increasing it if rifampicin lowers it [20].

Malnutrition and tuberculosis (TB) have a bidirectional relationship, complicating clinical assessments of which condition precedes the others. Our case involved treating the patient with F-75 and F-100 formulas, following the WHO guidelines for severe acute malnutrition [21], and addressing hypoalbuminemia with FFP. Anticoagulants and anti-TB therapy were administered for six months (ERHZ for 2 months and RH for four months), with careful monitoring of INR, liver function tests, and ultrasounds. At the follow-up clinic, the child’s condition was stable and all medications had been stopped.

Conclusion

The intricacy of TB is demonstrated by this case of disseminated TB in a pediatric child who presented with severe malnourishment, an enterocutaneous fistula, and deep vein thrombosis. Effective management required a multidisciplinary strategy that included anticoagulant therapy, nutritional rehabilitation, and conservative fistula care.It emphasizes how crucial it is to identify atypical TB symptoms and the need for prompt diagnosis and treatment in order to enhance results and avoid complications in children who are impacted.

Differential diagnosis for discharge through the umbilicus

1. Patent Vitello-Intestinal Duct: This congenital condition occurs when the duct connecting the yolk sac to the intestine fails to close after birth, potentially causing umbilical discharge, gastrointestinal bleeding, or abdominal pain. In our case, ascites, a positive gene Xpert for MTB, and a negative post-IV contrast CT scan for a vitelline duct or cyst challenged this diagnosis.

2. Pilonidal Cyst: Although a pilonidal cyst can drain near the umbilicus, it is more common in older children and young adults. The patient’s post-IV contrast CT, which showed no cyst, contradicts this possibility.

3. Infection with Abscess Formation: An abscess near the umbilicus can cause a pus-like discharge due to localized infection. However, the presence of fecal matter in the discharge and the negative post-IV contrast CT for localized abscess collection did not support this diagnosis.

Abbreviations

BMI

Body Mass Index

Cr

Creatinine

CT

Computed Tomography

CXR

Chest xray

DVT

Deep venous Thrombosis

ECF

Enterocutaneous Fistula

ERHZ

Etambutol, Rifampicin, Isoniazid, Pyrazinamide

FBS

Fasting Blood Sugar

F-75

Formula-75

F-100

Formula-100

FNAC

Fine Needle Aspiration Cytology

Ht

Height: LAPs: Lymphadenopathys

LFT

Liver Function Tests

MTB/RIF

Mycobacterium Tuberculosis and Rifampicin resistance

RBS

Random Blood Sugar

INR

International normalized ratio

RFT

Renal Function Test

RUQ

Right Upper Quadrant

RUTF

Ready to use therapeutic Feeding

SAM

Severe Acute Malnutrition

TB

Tuberculosis

UFH

Unfractionated Heparin

U/S

Ultrasound

U/L

Unit per Liter

WBC

White Blood Cells

WFH

Weight For Height

WHO

World Health Organization

Author contributions

AB was involved in the evaluation, investigation and treatment of the patient, report and manuscript writing; TT was involved in conception to report as a case, treating the patient, report and manuscript writing.DD was involved in investigating the patient, report, and manuscript writing.

Funding

There is no funding to report.

Data availability

Data are provided within the manuscript or supplementary information files.

Declarations

Ethical approval and consent to participate

The patient’s father provided written informed consent for participation and the use of the patient’s clinical information and photos in this case report. Every technique was used in conformity with the Declaration of Helsinki, which recognizes vulnerable groups and respects people’s freedom to make educated decisions. This case report does not require ethical clearance in accordance with the university’s criteria.

Consent for publication

For this case report to be published, written informed consent for publication of the patient’s clinical details and/or clinical images was obtained from the patient’s father. A copy of the consent form is available for review by the Editor of this journal.

Competing interests

The authors declare no competing interests.