Cronkhite-Canada syndrome complicated with pulmonary embolism: A case report

Abstract

BACKGROUND

Cronkhite-Canada syndrome (CCS) is a rare disease, that causes gastrointestinal polyps, ectodermal abnormalities, and gastrointestinal symptoms. CCS is prone to thromboembolism, but clinical workers have not yet established a clinical consciousness of preventing thromboembolism. The present case illustrates pulmonary embolism (PE) complicated by CCS.

CASE SUMMARY

A 46-year-old male patient presented with mucus, purulent, and bloody stool. Ectodermal changes included skin pigmentation, alopecia, and nail dystrophy. Colonoscopy revealed the presence of multiple polyps. After a comprehensive evaluation, the patient was diagnosed with CCS. During the disease, he was also diagnosed with pulmonary embolism, Riehl's melanosis, and intestinal flora imbalance. After symptomatic treatment with omeprazole, mesalazine, rivaroxaban, nutritional support, and regulation of intestinal flora, the patient’s symptoms were significantly relieved.

CONCLUSION

CCS complicated with PE was reported for the first time in China in this study. Despite the fact that CCS is extremely rare, patients with CCS should be classified as a high-risk venous thromboembolism (VTE) population, and emphasis should be placed on venous thromboembolism risk assessment and stratification, deep venous thromboembolism screening, prevention of VTE, and careful long-term follow-up.

Key Words: Cronkhite-Canada syndrome; Pulmonary embolism; Hip arthroplasty; Venous thromboembolism; Case report

Core Tip: The case report is a rare and complex case of Cronkhite-Canada syndrome (CCS) with pulmonary embolism. We completely recorded the whole process of the occurrence and development of the CCS and carried out follow-up observation. Without hormone treatment, the disease was cured through routine treatment. Patients with CCS have a higher risk of developing venous thromboembolism. We put forward a new view that patients with CCS should focus on preventing the occurrence of venous thromboembolism.

INTRODUCTION

Cronkhite-Canada syndrome (CCS) is a rare disease characterized by systemic gastrointestinal polyps and ectodermal abnormalities, including pigmentation, hair loss, and nail dystrophy, accompanied by different gastrointestinal symptoms[1]. CCS is sporadic and rare, with only 500 cases reported worldwide[2]. CCS is generally considered to be a chronic inflammatory disease associated with autoimmune mechanisms. There is currently significant evidence including ANA-positive, elevated IgG4 levels in blood circulation, polyps infiltrating IgG4-positive plasma cells, and clinically good response to immunosuppressive therapy[3-5]. Currently, there are no internationally recognized diagnostic criteria or systematic treatments.

In addition, pulmonary embolism (PE) is a common and potentially fatal disease worldwide, and its incidence increases with age[6]. A 100000 person is estimated to have 100-200 cases of PE[7]. The underlying mechanisms of PE are closely related to blood coagulation, endovascular damage, and inflammation[8]. An undamaged vessel develops a thrombus when inflammation in the vessel wall triggers coagulation and inflammation simultaneously, resulting in PE[9]. A basic study reveals the potential role of the innate immune response in the pathogenesis of CCS[10]. A variety of immune system elements play a role in the underlying inflammation associated with PE, including cytokines, leukocytes, and chemokines[11]. Although CCS is extremely rare, patients with CCS have a higher risk of developing venous thromboembolism (VTE)[12]. For the first time, China reported a case of CCS complicated with PE and provided a treatment plan during hospitalization.

CASE PRESENTATION

Chief complaints

A 46-year-old Chinese man was hospitalized for mucopurulent bloody stools.

History of present illness

In early September 2023, the patient occasionally experienced nausea, acid regurgitation, abdominal distension, and appetite loss. The patient was not diagnosed or treated. On October 17, 2023, the patient developed diarrhea, and mucopurulent bloody stool, accompanied by acute and severe sensations, and the recent weight loss was about 5 kg. He was administered antidiarrheal drugs, but the symptoms were not relieved.

History of past illness

Patients with a history of hypertension for 4 years, long-term oral irbesartan capsules. His blood pressure is well controlled. On September 22, 2023, the patient underwent right hip arthroplasty at a local hospital and received oral rivaroxaban for a long time after the operation. On September 28, 2023, the patient was diagnosed with pulmonary embolism.

Personal and family history

The patient has smoked for more than 30 years, approximately 20 cigarettes per day, and there is no family history of this patient.

Physical examination

Physical examination showed a heart rate and blood pressure of 110 beats/minute and 130/70 mmHg, respectively, and a respiratory rate of 20 breaths/minute. The body mass index was 22 kg/m². Poor spirits, sparse hair, dystrophic nails, and dark brown pigmentation on the face, palms, and feet, were present in the patient (Figure 1).

Figure 1 The physical examination we found that the patient had alopecia, onychodystrophy, and skin pigmentation. A: The region of the head; B: Palms; C: Soles.

Laboratory examinations

Abnormal laboratory tests results are presented in Table 1. HIV, syphilis, and hepatitis B and C were all negative, and no abnormalities were found in serum amylase, procalcitonin, thyroid function (TSH, FT₃, and FT₄), or five immune items (IgA, IgG, IgM, C3, C4). No abnormalities were found in fecal samples, and Salmonella, Shigella, and fungi were not detected in general bacterial culture in feces.

Table 1 Abnormal laboratory results after admission.

Parameter	On admission	Normal range
Hematocrit (L/L)	0.398	0.40–0.50
Average platelet Distribution width (%)	9.1	10.0–30.0
Monocyte percentage (%)	12.4	3.0–10.0
Monocyte count (× 109/L)	0.9	0.1–0.6
Eosinophil count (× 109/L)	0.56	0.02–0.52
C-reactive protein (mg/L)	39.76	0–10
D-dimer (mg/L)	1.10	0–0.55
Prothrombin time (s)	13.30	9.8–12.1
Fibrinogen (g/L)	6.58	1.8–3.5
Uric acid (μmol/L)	530.5	208–428
Calcium (mmol/L)	2.67	2.11–2.55
Magnesium (mmol/L)	0.66	0.7–1.0
Phosphorus (mmol/L)	1.68	0.81–1.45
Creatine kinase (U/L)	28.8	55–170
Troponin (ng/mL)	0.017	0–0.014
Lactic acid (mmol/L)	3.9	0.7–2.1
Globulin ratio (g/L)	1.1	1.2–2.4

Imaging examinations

Colonoscopy revealed that the left colon was dominated by red hyperplastic polyps. The sigmoid colon from 15 to 20 cm at the entrance of the anus showed hyperplastic polyps growing in the circumferential cavity, and the surface of the polyps was congested. There were mainly mucosal scars in the right colon, and red sessile polyps diffused into the intestinal cavity (Figure 2). A biopsy of the sigmoid colon showed chronic inflammation of the intestinal mucosa with polypoid hyperplasia, proliferative changes in glandular ducts, and abscess formation in individual lumens (Figure 3).

Figure 2 Enteroscopy. A-C: The sigmoid colon: the mucosa of the whole colon was rough, and the left colon was dominated by red polypoid hyperplasia. The sigmoid colon from 15 cm to 20 cm at the entrance of the anus shows hyperplastic polyps growing in the circumferential cavity and the surface of the polyps is congested; D-F: Descending colon: there are mainly mucosal scars in the right colon, and red sessile polyps are diffused in the intestinal cavity.

Figure 3 Histological photos of endoscopic biopsy specimens taken from the colon. A biopsy of the sigmoid colon tissue showed chronic inflammation of the intestinal mucosa with sarcoid hyperplasia, glandular proliferative changes, and the formation of abscesses in individual lumens (hematoxylin-eosin staining, × 100).

FINAL DIAGNOSIS

The patient was diagnosed with the following: (1) CCS; (2) pulmonary embolism; (3) intestinal dysbiosis; (4) hypertension; (5) rash; and (6) history of hip replacement surgery (right) (ICD-11).

TREATMENT

After admission, the patient was treated symptomatically and supportively, with nutritional support (Vitamin B₆ and Vitamin C), gastric mucosal protection (rabeprazole sodium enteric-coated tablets), and regulation of intestinal flora (live combined Bifidobacterium and Lactobacillus tablets). This patient was administered dehumidifying and antipruritic ointment to treat the rash. After discharge, the patient was treated with live combined Bifidobacterium and Lactobacillus tablets and compound glutamine. The patient continues to take oral rivaroxaban and irbesartan.

OUTCOME AND FOLLOW-UP

After 1 month of treatment, the patient came to our hospital for a re-examination, we found that the patient's diarrhea and blood in stool symptoms were completely relieved, the rash subsided, and he gained 2 kg. As ectodermal and digestive symptoms resolved, we recommended discontinuing live combined Bifidobacterium and Lactobacillus tablets and compound glutamine. Rivaroxaban was discontinued as the pulmonary embolism was no longer present. After 3 months, the patient’s skin color was normal and his nail dystrophy was improved. We advised the patient to undergo a gastroenteroscopy, but the patient declined the examination.

DISCUSSION

Cronkhite and Canada first proposed a clinical description of CCS in 1955[13]. One in a million people suffer from CCS, a rare non-hereditary disease[14]. All ethnic groups are susceptible to CCS, but Europeans and Asians are the most commonly affected, with most cases occurring in Japan[14,15]. The age of onset is mainly between 50 and 70 years old[15].

However, the etiology and pathogenesis of CCS remain unclear. A study finds that CCS is often associated with autoimmune diseases and IGg4 plasma cell infiltration, so CCS may be an autoimmune disease[16]. In another study, psychological stress was found to cause local inflammation of the gastrointestinal mucosa, and three patients improved even after only reducing anxiety stress[17]. Approximately 54% of CCS patients also suffer from Helicobacter pylori (Hp) infection, but after eradication of Hp, the clinical symptoms and gastrointestinal endoscopic manifestations are significantly relieved, indicating that there is a certain relationship between Hp and CCS[18,19]. It has also been reported that CCS is associated with intestinal flora imbalance[20].

Currently, there is no unified standard for CCS treatment. Corticosteroids, azathioprine, various antibiotics, rabeprazole, infliximab, and symptomatic treatment have been used in patients. It is reported that a CCS patient with remission induced by prednisone and maintained by azathioprine was successfully cured[21]. One CCS patient with Hp infection was relieved after eradication of Hp and adjustment of intestinal flora[20]. The clinical symptoms of one patient with refractory CCS were completely relieved, and gastrointestinal polyps disappeared significantly after induction and maintenance treatment with infliximab[22]. Oral corticosteroids are the best treatment for CCS, providing relief of abdominal symptoms within a few months and causing polyps to disappear in over 6 months[23]. However, one patient with CCS developed pulmonary embolism after using glucocorticoids, and pulmonary artery and distal vein thrombosis occurred repeatedly after sufficient anticoagulation time[12]. Some studies have also found that patients using glucocorticoids have an increased risk of thromboembolism[24,25]. Therefore, patients are currently treated with anticoagulant therapy and long-term follow-up to evaluate their condition and develop a CCS treatment plan.

To date, the risk of thromboembolism in CCS has not been determined. The patient had ectodermal changes such as alopecia, nail atrophy, and skin pigmentation before hip arthroplasty, and was routinely treated with rivaroxaban after the operation. However, the patient was diagnosed with pulmonary embolism on the 6th day after the operation. Patients take anticoagulants regularly after surgery but still have pulmonary embolism. Autoimmune and chronic inflammatory diseases are known to be a risk factor for VTE[26]. CCS is considered a chronic inflammatory disease, which is enough to suggest that CCS induces VTE. An association has been established between inflammation and thrombosis in numerous clinical scenarios, and inflammatory processes are related to abnormal coagulation[27]. Some inflammatory biomarkers such as eosinophils, monocytes, and C-reactive protein may be potential risk factors for VTE[28-30]. Some studies have also shown that although CCS is rare, there is a higher risk of developing VTE, especially with surgical intervention[27]. Before the thrombotic event, our patient underwent a hip replacement that exacerbated his inflammatory state. He was in a hypercoagulable state with elevated levels of fibrinogen and D-dimer, suggesting venous thrombosis.

By studying this case, we know that patients with CCS should fully strengthen the prevention of thromboembolism, especially in cases of large traumatic surgeries such as hip arthroplasty. Therefore, when patients show signs and symptoms consistent with CCS, clinicians should suspect the disease and perform gastroenteroscopy. If CCS is diagnosed, thromboembolism prevention should be started immediately, and careful long-term follow-up should be performed, which is helpful for the treatment and prognosis of the disease. However, at present, the risk of pulmonary embolism in patients with CCS has not been determined, and whether there is a difference in the risk of pulmonary embolism between patients with CCS undergoing hip arthroplasty and those without CCS needs further study.

CONCLUSION

In summary, we present a case of pulmonary embolism caused by hip arthroplasty in the patient with CCS. Although CCS is rare, patients with CCS have a high risk of pulmonary embolism, considering what is currently known. When patients have ectodermal symptoms of CCS, gastroenteroscopy should be performed to further carry out thromboembolism risk assessment and stratification, deep vein thrombosis screening, prevention of potential arteriovenous thrombosis, and to reduce the risk of VTE in patients with CCS.

ACKNOWLEDGEMENTS

The authors would like to thank Dr. Yanqiu Xu and Dr. Xinxin Zhang, for their assistance during hospitalization in this case.