Unexpected Pneumomediastinum in Crohn’s Disease: Implications and Case Analysis

Introduction

Inflammatory bowel disease (IBD) is a group of autoimmune diseases that are characterized by inflammation of the small and large intestines, in which elements of the digestive system are attacked by the body’s own immune system, and under that umbrella of disease, Crohn’s disease and ulcerative colitis are included [1,2]. The etiology of IBD is not well-established; however, the interaction of environmental and immunoregulatory factors in genetically vulnerable individuals is thought to be the leading contributor [3–5].

Common symptoms of IBD include diarrhea, blood loss from the intestines, and abdominal pain [6]. It has been found that the most common presenting symptoms in Crohn’s disease are fatigue and abdominal pain, while in ulcerative colitis, bloody bowel movements and diarrhea are most common [7]. There are reported cases of extra-intestinal manifestations, most commonly in the musculoskeletal and dermatologic systems. Many patients with IBD present with abnormal liver chemistries, and identifying the etiology can be challenging because the differential diagnosis is broad and 2 or more diseases can co-exist [7,8]. Presentation with pneumomediastinum and subcutaneous emphysema is rare, and is often induced by endoscopies and colonoscopies [9,10]. Presentation with pneumomediastinum is extremely rare and is linked with the severity of colitis [9–13].

Here, we report the case of a patient with diarrhea, abdominal pain, an incidental finding of pneumomediastinum, and severe colitis shown by images and scopes, which was then confirmed histologically to be Crohn’s disease, an inflammatory bowel disease. Clinical practitioners need to have high clinical suspicion in such scenarios and address the complexities of autoimmune diseases, which still show new features from time to time. They also need to consider other pathophysiological processes of this presentation not mentioned in previous reports, which need to be further assessed.

Case Report

A 23-year-old woman with background of subfertility with unclear cause and iron-deficiency anemia but not on any medication had presented 14 days earlier to the emergency department (ED) of another hospital with severe constipation and lower abdominal pain. Initially, she was investigated for signs of infection and abdominal X-ray and ultrasound were done, which produced normal results. She was given a laxative in the ED and discharged home.

Although she did not take any more laxatives thereafter, she started to have severe diarrhea that continued until she presented to our ED 14 days later. The diarrhea occurred more than 10 times per day, was watery and sometimes had bloody streaks but no mucous contents. This was associated with generalized severe abdominal pain, nausea, and vomiting 2 times, as well as low oral intake and fever. She was feeling lethargic and had a headache, but had no visual or other neurological symptoms. She denied any chest pain, shortness of breath, palpitation, cough, flu symptoms, or sore throat. She did not have joint or skin concerns. She denied any oral ulceration, perianal pain, or ulcers. This was the first such episode in her life. Results of the other systematic exams were unremarkable. Her family history was unremarkable for any gastrointestinal inflammatory, malignant disease, genetic or rheumatological diseases, and nobody else in the family had the same symptoms at that same time. She denied unusual food intake, travel, sick contact, or animal contacts.

On examination, she looked very tired and lethargic, with significant dehydration. She was thin, with body weight 50 kg, her temperature was 38.4°C, heart rate 140 beat/min, and blood pressure 122/73, and she was maintaining 100% saturation on room air, with tachypnea of 23 to 30 breath/min. An abdominal examination revealed significant tenderness all over, but no rebound, organomegaly, or palpable mass. Bowel sounds were active and the abdomen was soft and not distended. There were no oral ulcers, eye changes, or any skin or joints changes. Chest examination was normal with normal breath sounds and cardiovascular examination was normal with normal S1, S2, and no murmurs. She has no signs of deep vein thrombosis and her neurological examination was otherwise normal. Her initial blood glucose level was 8.8. Urine dipstick showed 1+ ketones, and the rest were nil. A pregnancy test was negative. Her initial venous blood gas assessment was normal.

The initial CT abdomen and pelvis showed a thickened wall of the rectum, sigmoid, and descending colon, and to a lesser extent the transverse colon, suggestive of colitis and diffuse hepatic steatosis.

Her laboratory investigations showed hemoglobin of 8.6 g/dL (it was 9.5 g/dL at the previous visit), white blood cell count 8.4×109/L (previously 12.5×109/L), absolute neutrophils count (previously 6.5×109/L), C reactive protein 111 (previously 68), and platelets 850×109/L. Peripheral blood film analysis did not show schistocytes or any features of concern. Serum sodium was 127 mmol/L (135–145), potassium 5.1 mmol/L (3.5–5.1), creatinine 46 umol/L, urea 1.4 mmol/L, chloride 86 mmol/L, bicarbonate 27 mmol/L, anion gap 11 mmol/L, alanine aminotransferase (ALT) 13 U/L (0–33), aspartate aminotransferase (AST) 10 U/L (0–32), alkaline phosphatase (ALP) 103 U/L (35–104), bilirubin 10 umol/L (0–17), albumin 19 g/L (35–52). Magnesium was 0.66 mmol/L (0.66–1.07), phosphate was 0.76 mmol/L, and calcium was 1.7 mmol/L.

She was started on ceftriaxone with the impression of possible infective colitis. She received more than 3 L of intravenous fluid hydration and was kept on maintenance hydration 120 ml/h of normal saline. Pan-cultures was sent from urine, blood, and stool, along with viral screen SARs-CoV-19, other respiratory viruses, gastrointestinal viruses, retroviruses, and Clostridium difficile, which were all negative.

On day 2 she remained persistently tachycardiac and lethargic with generalized weakness and significant lower-limb pitting edema; therefore, the care team was worried about missing a critical diagnosis like nephrotic syndrome complicating gastroenteritis and causing pulmonary embolism or pulmonary embolism due to immobilization and severe dehydration.

Electrocardiography showed sinus tachycardia with no other worrisome signs. Her protein creatinine ratio was normal, which ruled out concerns of nephrotic syndrome, but her D dimer was high at 1.7 mg/L (normal: 0.2–0.7), so we proceeded to CTPA, which revealed right lower-lobe segmental and sub-segmental non-occlusive pulmonary embolism with no CT evidence of right ventricular strain. There was mild-to-moderate diffuse esophageal thickening suggestive of esophagitis and mild pneumomediastinum (Figure 1). Doppler imaging of the lower limbs did not show any sign of deep venous thrombosis.

Due to the CT finding of a pneumomediastinum, the team re-examined her for any signs of trauma and reviewed any history of falling, intent to self-harm, or psychological issues, but all were negative.

The general surgeon was involved immediately, as well as gastroenterologist, and the patient was taken immediately to an operating room for suspicion of Boerhaave syndrome. Gastrografin swallow assessment ruled out a local leak as cause of the pneumomediastinum.

Before performing a Gastrografin swallow, the patient became unresponsive and was hypoglycemic (1.4), for which 50 ml 50% dextrose was given and she was kept on dextrose water thereafter, which helped her regain consciousness and improved her overall generalized weakness.

For re-evaluation of her new deterioration, all basic laboratory tests, coagulation, and cultures was repeated, showing a further drop in hemoglobin to 7.7 g/dL, low haptoglobin (1.4), increase in LDH from 316 U/L to 1095 U/L, bilirubin 19 umol/L, significant derangement in her liver enzymes and function (ALT 52 U/L, ALP 113 U/L, AST 70 U/L, albumin 14 g/L, INR 3.45, PT 35, aPTT 50.7, fibrinogen 2.3), and significant fast rise in lactate to a maximum of 11.1 mmol/L. She started to develop high anion gap metabolic acidosis with respiratory compensation (HCO3 15, CO2 21, pH 7.39, anion gap 26), and developed a second episode of hypoglycemia down to 2.5.

Her creatinine kinase went up to 553 U/L and electrolytes were low at Ca 1.76 mmol/L (2.15–2.55) and low PO4 0.76 mmol/L (0.81–1.45), consistent with acute liver injury (MELD Na 25.3) (Figures 2, 3: LFT and INR trends).

All of the above deteriorations suggested acute liver injury, with possible drugs, herbs, alcohol, infections, autoimmune diseases, vascular thrombosis, and genetic or metabolic causes.

Based on that, her paracetamol level was tested and was slightly high (> 20 umol), but she was receiving regular QID doses of 1 g IV paracetamol. She denied alcohol, herb, or IV drugs intake. An infectious diseases workup was negative, including acute hepatitis screen, CMV, EBV, HSV, VZV, parvovirus B19 virus, adenovirus, malaria, leptospira, brucella, Coxiella burnettii, and amoebiasis. An autoimmune workup was negative, including ANA, dsDNA, ENA, ANCA, autoimmune hepatitis, lupus anticoagulant, antiphospholipid antibodies, thyroid antibodies, celiac screen, ceruloplasmin, alpha-1 antitrypsin, and thrombophilia workup. Fecal calprotectin was very high at 2097 mg/kg (normal 1–50). Ferritin was 450, and hemochromatosis gene analysis (HFE) was negative.

CT angiography abdomen was done for reassessment and to rule out hepatic or bowel vasculature thrombosis, which re-demonstrated thickening of rectum, sigmoid, left descending colon, and transverse colon, including the hepatic flexure, with interval involvement of the ascending colon associated with minimal adjacent fat stranding and mild engorgement of the adjacent mesenteric vessels. No vascular filling defect was found.

She was started empirically on acetylcysteine, vitamin K, fresh frozen plasma, and thiamine, and the antibiotics were upgraded to meropenem, metronidazole, and anidulafungin to cover any possibility of candida esophagitis or mediastinitis.

Before the scope and fecal calprotectin results were available, the metabolic and genetic team was contacted to rule out fatty acid oxidation defects and mitochondrial or genetic diseases, and the patient was kept on IV dextrose. All metabolic and genetic investigations came back negative.

She was then immediately shifted to the intensive care unit from the high-dependency unit for closer observation and we had a discussion with the patient and her family about the need to prepare for liver transplant due to this acute unexplained deterioration, but they refused.

On the third day in our ICU (hospital day 5) her liver function was still worsening, so empiric methylprednisolone 40 mg bid was started. By next day of starting steroids her liver function started improving with improvement in all over her clinical features. That correlated improvement with steroids, overall clinical presentation and further literature review of pneumomediastinum correlation with IBD, the team suspicion was higher for IBD and so proceeded to upper and lower endoscopy.

Esophago-gastroduodenoscopy (OGD) showed a normal esophagus, stomach, and duodenum. Biopsy results were normal. Colonoscopy showed scattered longitudinal deep ulcers in the rectum, sigmoid colon, descending colon, transverse colon, and ascending colon, with severely erythematous mucosa giving cobblestone appearance, diffuse edema, and multiple pseudo-polyps and exudates, so multiple biopsies were taken. The cecum and terminal ilium had unremarkable mucosal findings. These findings indicate severe IBD, consistent with Crohn’s disease colitis (Figure 4).

The histopathological report confirmed IBD. Biopsies of the ascending colon and rectum showed chronic colitis with ulceration, inflamed granulation tissue formation, architectural distortion, focal cryptitis, crypt abscess formation, and Paneth cell metaplasia, and the biopsy was negative for granuloma, dysplasia, or malignancy. MRI of the liver showed a fatty liver and diffusely edematous pancreas with loss of normal lobulations, with peri-pancreatic fat stranding consistent with autoimmune pancreatitis.

After endoscopy, the patient was started on regular doses of 20 mg TID methylprednisolone and observed for 4 days. She was then discharged with an impression of severe fulminant Crohn’s disease with severe liver injury, colitis, and pneumomediastinum, and the prednisolone dose was tapered by 5 mg every week starting at 40 mg once daily. Rivaroxaban 20 mg od was prescribed for 6 months due to the pulmonary embolism.

One month later, she was seen in an outpatient clinic and noted remission of her clinical and biochemical features. Adalimumab induction 160 mg followed by 80 mg 2 weeks later and 40 mg there after every 2 weeks along with azathioprine 50 mg od was initiated. On follow-up 3 months later, she was pregnant, so anticoagulation was extended all through the pregnancy duration, with close follow-up with the hematologist, gastroenterologist, and obstetrician.

Discussion

Inflammatory bowel disease is a chronic immune-mediated disorder that includes Crohn’s disease and ulcerative colitis. It is a multisystem disorder that affects predominantly the gastrointestinal tract. Extra-intestinal manifestations are widely reported and occur in 6% to 47% of cases [14]. Pneumomediastinum, which is defined as air present in the mediastinum, is a rare clinical condition [15] and is rarely reported in IBD patients [10,16]. It can be seen on simple CXR or on CT chest. The main symptom is chest pain, occurring in 60% to 100% of presentations; however, shortness of breath is also common and is present in 75% of cases [15,17].

The causes of pneumomediastinum are either secondary to blunt chest trauma or underlying lung pathology like asthma, COPD, or bronchiectasis [17]. Other secondary causes include complicated emphysematous pyelonephritis iatrogenic procedures like bronchoscopy, upper and lower gastrointestinal endoscopies, central line insertion, and intubations [17,18]. If no identifiable cause is detected, then it is referred to as spontaneous pneumomediastinum, although some authors prefer to call this type of pneumomediastinum primary (very rare), since it allows a better differentiation from secondary (very common) pneumomediastinum. For most authors, in the absence of trauma, any factor leading to pneumomediastinum (whether predisposing, precipitating, or both) is classified as spontaneous (primary), which contradicts their own definition [19].

Few reported cases have been described in the literature regarding pneumomediastinum and inflammatory bowel disease. Most of these cases were already diagnosed as IBD, especially ulcerative colitis [10,16,20–22]. However, there has been 1 case report of pneumomediastinum in a patient who presented with a flare-up of Crohn’s disease [10]. Other case reports also described pneumomediastinum in IBD after interventions like colonoscopy, and others were correlated with long-term steroids use that induced bowel perforation and pneumomediastinum [23,24].

The link between IBD and pneumomediastinum is the severity of the disease [10,22]. The proposed mechanism in inflammatory bowel disease is that severe inflammation facilitates forcible herniation of the colonic mucosa, allowing microscopic perforations to develop that are permeable to air [10]. This microscopic air leaks to the retroperitoneum, which communicates with the mediastinum through the visceral space, resulting into pneumomediastinum and can extend up to the neck [18,25].

Our patient presented a diagnostic dilemma as she was admitted in relatively stable condition and then rapidly progressed to multisystem involvement, including the gastrointestinal tract, liver, chest, kidneys, and blood. Her CT pulmonary angiography showed pneumomediastinum before any procedural interventions or endoscopy and before steroids initiation. She was subsequently diagnosed with Crohn’s disease, highlighting the rarity and challenges in ultimately reaching this diagnosis. In addition, pneumomediastinum has been reported mainly in cases of ulcerative colitis and only 1 case report has been linked to Crohn’s disease. However, our case was similar to other case reports in that pneumomediastinum was linked to the severity of the colitis. The patient improved after starting steroids and subsequent immunosuppressive medications.

Conclusions

Pneumomediastinum is a rare manifestation of inflammatory bowel disease, which could be reflective of severe colitis and should be considered in patients presenting with chest symptoms regardless of procedure, scope exposure, or long-term steroids use. Attention to early instability signs like tachycardia and tachypnea can help reveal early complications and anticipate further deteriorations.