A Case Report and Literature Review on Systemic Sclerosis Manifesting as Melena and Hematochezia

Abstract

Systemic sclerosis (SSc) is a rare autoimmune disorder that leads to progressive fibrosis and vascular dysfunction, frequently affecting the gastrointestinal tract with around 90% of patients experiencing gastrointestinal complications, with severe manifestations such as gastric antral vascular ectasia and rectal telangiectasia which lead to chronic bleeding and iron-deficiency anemia. This review and case report explore the pathophysiology of GI involvement in SSc, emphasizing fibrosis, microvascular damage, and dysmotility. It also highlights treatment options, including endoscopic interventions like argon plasma coagulation and pharmacological therapies.

Introduction

Systemic sclerosis (SSc), also known as scleroderma, is a rare and complex autoimmune connective tissue disease marked by vascular dysfunction, immune dysregulation, and progressive fibrosis affecting various organs, like the skin, and internal organs including the gastrointestinal tract,^1-15 lungs,^7,10,12 heart, and kidneys. ¹ GI tract involvement is the second most common manifestation after skin involvement, occurring in around 90% of patients^1-24 making GI complications the fourth leading cause of death in SSc, particularly in patients with diffuse skin involvement. ² These affect mostly the esophagus, liver, ⁵ small intestines, and the rectum, ¹ leading to esophageal motility disorders, dysphagia, ⁷ gastroesophageal reflux disease (GERD),^24-27 constipation, and diarrhea. ⁷ As fibrosis and vascular damage further progress, they lead to gastric antral vascular ectasia (GAVE), and telangiectasias, both of which can lead to GI bleeding and iron deficiency anemia. ³ GAVE, also known as “watermelon stomach” affects between 5.7% and 22.3% of SSc patients across studies.^9,21,22 Rectal telangiectasias, rarely reported in studies compared to other complications of SSc, consist of another vascular complication which can contribute to fresh blood in stool. ¹ These are due to the presence of dilated capillaries in the rectum. ¹

Case Report

In this case report, we describe a patient with known SSc who presented with GI bleeding, melena, and fresh blood in the stool. GAVE and rectal telangiectasia were both detected via endoscopy. The patient was successfully treated with argon plasma coagulation (APC) and recovered without complications.

Case Presentation

A 69-year-old female patient with a 10-year history of SSc presented to the emergency department with a 3-day history of melena and recurrent passage of fresh blood in the stool. She does not have abdominal pain, nausea, vomiting, or noticeable weight loss but did claim minor dizziness and fatigue for a few days. There was no history of nonsteroidal anti-inflammatory medication use or anticoagulant therapy. Her medical history included a 10-year-old diagnosis of limited cutaneous SSc, esophageal dysmotility, and Raynaud’s phenomenon. Family history was irrelevant with no bleeding disorder nor GI malignancies. The patient denied alcohol use and has no known food or drug allergies.

Upon physical examination, the patient was found to have pale conjunctiva, with a delayed capillary refill time, but hemodynamically stable, with a heart rate of 92 beats per minute (N: 60-100 bpm) and a blood pressure of 110/70 mmHg (N: 90/60-120/80 mmHg). There was no discomfort, tenderness, or organomegaly found during the abdominal examination. Digital rectal examination revealed bright red blood and melena, but no palpable masses.

Laboratory Values

The results of laboratory tests revealed a normal platelet count, normal coagulation profile, and a hemoglobin level of 8.5 g/dL (down from a baseline of 12 g/dL; N: 12-18 g/dL). Renal and liver function tests were within the normal ranges. The presence of blood was confirmed through a stool guaiac test.

Differential Diagnosis

The differential diagnosis for a patient with SSc who presented with melena and rectal bleeding was as follows:

• ■ “Watermelon stomach,” or GAVE, a disorder related to SSc that can result in upper GI bleeding.

• ■ Gastric ulcers or esophagitis, which are frequently experienced by people with SSc as a result of GERD.

• ■ Rectal or colonic telangiectasia, a vascular manifestation of SSc that can result in bleeding in the lower GI tract.

• ■ Colorectal cancer or diverticular disease, which should be taken into consideration considering the rectal bleeding even if there were no further symptoms that strongly suggested these diagnoses.

• ■ Colon angiosplasia, which is frequently linked to vascular lesions and potential lower GI hemorrhage.

• ■ Hemorrhoids are less likely possible since the presence of melena.

Investigation

The patient underwent panendoscopy to determine the source of the bleeding. It showed a normal esophagus with no evidence of esophagitis, stricture, varices, tumor, Barrett’s, or any other esophageal abnormality except for patulous gastroesophageal junction on retroflection. A 10 mm fundic gland polyp was found in the body of the stomach. In the body to the antrum, the presence of characteristic longitudinal red stripes (Figure 1) is consistent with GAVE.

Figure 1.

Snapshot from colonoscopy showing several linear erythematous mucosae.

Treatment

APC was used to treat both rectal telangiectasia and GAVE lesions. This technique has been chosen for its effectiveness in managing bleeding from vascular lesions by using a regulated plasma energy beam that causes the injured tissue to clot. The patient had no immediate or delayed complications, and the treatment was well tolerated.

Outcome

Following treatment, the patient’s hemoglobin normalized, and she had no further melena or rectal bleeding. She was discharged home in stable condition, with a potential repeat endoscopy scheduled if further bleeding occurred, as well as thorough monitoring of her SSc. To treat her autoimmune condition and the possibility of more GI bleeding, routine follow-up visits with her gastroenterologist and rheumatologist were advised. A repeat upper endoscopy was performed and it was unremarkable.

Discussion

Pathophysiology of GI Involvement

SSc is subdivided into 2 main types based on the extent of skin involvement: limited cutaneous SSc which affects the face, hands, and forearms, and diffuse cutaneous SSc (dcSSc) which involves more skin involvement as well as severe internal organ complications.^1,15,21 Notably, GAVE can occur in both types of SSc with an earlier presentation in the disease course in patients with dcSSc. ²¹ The multifactorial pathophysiology of GI involvement in SSc is primarily driven by smooth muscle atrophy, fibrosis, and vascular damage.^3,4,8 Microvascular dysfunction, a hallmark in that complex etiology, affects several organs in the GI tract. ¹³ Endothelial cell damage leads to chronic hypoxia and ischemia in the microcirculation, which in turn causes dysmotility and vascular diseases such as telangiectasia and GAVE.^6,13 On the other hand, progressive fibrosis and muscle damage are mediated by ischemia and immune-mediated inflammation due to the stimulation and differentiation of fibroblasts into myofibroblasts by transforming growth factor β leading to stimulation of extracellular matrix production and deposition of collagen.^3,12 Additionally, biomarkers like vascular endothelial growth factor (VEGF) are shown to be associated with vascular malformations. In the stomach, this manifests as GAVE, that results in dilated, fragile blood vessels in the stomach lining of the antral region that are consequently prone to rupture.^1,7,12,20,24 SSc-related vascular changes are also responsible for the development of telangiectasias along the GI tract,^1,3,5,6 including the rectum, further exacerbating GI bleed. Other associated conditions include GERD, esophageal dysmotility, and dysphagia; gastroparesis affecting stomach function^2,4,15,24; and various lower GI issues such as diarrhea, constipation, and anorectal dysfunction. Additionally, small intestinal bacterial overgrowth and pseudo-obstruction can occur,^2,3,4,7,24 all of which contribute to significant morbidity.

GAVE in SSc

Due to its characteristic appearance during endoscopy, GAVE, also known as “watermelon stomach,” presenting as dilated blood vessels radiating from the pylorus to the gastric antrum, is a major contributor to chronic GI bleeding and iron deficiency anemia in SSc patients.^{1,2,3,11,17,18,21,24} Its development is thought to be related to the damage to the microvasculature, disruption of local blood flow along with the proliferation of neuroendocrine cells and increased levels of vasoactive substances like prostaglandin E2 and serotonin. With a reported prevalence of up to 22.3%, GAVE is more common in individuals with cirrhosis and also occurs frequently in those with SSc. ²¹ Although re-bleeding is common and often requires repeated interventions, the first-line treatment for controlling GAVE-related bleeding is endoscopic therapy, particularly APC. It effectively coagulates by cauterizing fragile blood vessels, thereby stopping the bleeding.^17,18,24,25 Additional therapeutic options include endoscopic band ligation (EBL) and radiofrequency ablation (RFA), the results of which indicate comparable or superior efficacy for APC and RFA, particularly in cases of refractory or recurrent GAVE.^17,18 However, St Romain et al showed in a first retrospective analysis comparing between RFA and APC in patients with or without cirrhosis that RFA did not outperform APC despite the authors’ anecdotal experiences. ²⁵ In addition to APC, EBL, and RFA, cryotherapy and neodymium-doped yttrium aluminum garnet (Nd:YAG) laser photocoagulation have also been used to control GAVE-related GI bleeding. ¹⁹ Also, several case reports have documented using other procedures such as forceps endoscopic ablation and monopolar electrocoagulation with 5% polidocanol injection.^16,21 Although their outcomes are frequently successful, more research is required before making any firm conclusions.^16,21

Despite success rates of endoscopic treatments, recurrence and re-bleeding remain a major challenge in up to 42.7% of patients within 5 years, ¹⁶ which require ongoing monitoring. Interestingly, it has also been shown that among other biomarkers of SSc like anti-nuclear antibodies, present in more than 90% of SSc patients; anticentromere antibodies, anti-topoisomerase I, present in 15-25% of SSc patients, GAVE is strongly associated with anti-RNA polymerase III (anti-RNAP3) antibodies found in 10% to 25% of patients,^10-12 which may predict severe vascular involvement in SSc. Serling-Boyd et al, demonstrated that while anti-RNAP3 was the predominant autoantibody linked to GAVE, no significant relationship with other frequent SSc-specific autoantibodies, such as anti-Scl-70 or anti-centromere antibodies was found.^10,11,14

On the other hand, pharmacological treatment of GAVE includes several drugs such as octreotide, cyproheptadine, cyclophosphamide, prednisolone, estrogen-progesterone, thalidomide, bevacizumab, and tranexamic acid. ¹⁹ To note, these are more effective in cases of acute bleeding. Cyproheptadine, a first-generation antihistamine appears to help reverse iron-deficiency anemia in certain cases. ¹⁹ Better results were reported with corticosteroids and immunosuppressive therapy with cyclophosphamide which may be helpful in other autoimmune illnesses with GAVE. ¹⁹ In addition, according to some reference, cyclophosphamide is effective in refractory SSc-associated GAVE unresponsive to endoscopic treatment. ¹⁹ Estrogen progesterone therapy is another treatment option but has not been shown to eradicate ectatic vessels, emphasizing the fact that abruptly stopping the regimen may result in recurrent bleeding. ¹⁹ Furthermore, some case reports showed that thalidomide, an angiogenesis inhibitor, successfully stopped bleeding in patients whose lesions were resistant to endoscopic treatment. ¹⁶ That said, a monoclonal antibody called bevacizumab inhibits the antiangiogenic properties of VEGF A. Evidence suggests that it may decrease the need for endoscopic procedures and blood transfusions in GAVE patients.^19,27 Tranexamic acid is an antifibrinolytic drug that works by stopping the breakdown of fibrin and keeping clots structurally intact. ¹⁹ It is considered another useful option for stopping severe GAVE-related bleeding. To conclude, pharmacotherapy is not usually recommended as the only treatment and typically does not alter the endoscopic look of GAVE. ¹⁹

Finally, surgical interventions such as antrectomy, partial gastrectomy, total gastrectomy, and esophagogastrectomy are reserved for refractory patients when other treatments fail.^19,21

Management of GAVE is summarized in Figure 2.

Figure 2.

Management of GAVE. GAVE, gastric antral vascular ectasia; IDA, iron deficiency anemia.

Telangiectasia and Other Vascular Lesions in SSc

Another vascular manifestation of SSc, telangiectasia, consisting of dilated small blood vessels can occur anywhere throughout the GI tract.^5,7 However, these are more commonly encountered in the skin, stomach, and rectum which contributes to chronic GI bleeding usually requiring iron supplementation or blood transfusions. ¹⁶ The presence of telangiectasia in the GI tract emphasizes the systemic character of vascular disease in SSc. This has been demonstrated in several studies where up to 60% of GAVE patients will develop skin telangiectasia and compared to patients without small bowel angioectasia, those with small bowel angioectasia exhibited a significantly higher incidence of skin telangiectasia along with lower hemoglobin levels.^6,21

In terms of management, APC is effective in more localized lesions but may be challenging when the lesions are too in the GI tract which requires alternative approaches like supportive care including iron supplementation like low-frequency intravenous iron therapy and careful monitoring for upcoming bleeding episodes. ²⁶ Novel therapies, such as anti-angiogenic agents like bevacizumab, have been explored for managing these vascular lesions, though their use remains investigational. ¹⁹ As importantly, both polidocanol injection (PDI) and APC were highlighted as effective in the treatment of small bowel angioectasia. In cases with active bleeding, PDI was applied sometimes with APC in a retrospective study which showed excellent outcomes with no adverse effects or re-bleeding after treatment. ⁶

Diagnosis and Imaging

A combination of imaging techniques, laboratory testing, and clinical assessment is needed to establish the diagnosis of GI complications in SSc patients. Since endoscopy, also esophagogastroduodenoscopy, enables direct visualization and therapeutic intervention, it remains the gold standard for diagnosing telangiectasia and GAVE.^3,7,23 Small bowel involvement has been identified by capsule endoscopy and double-balloon endoscopy, which reveals the degree of vascular lesions and motility disorders that may not be evident with standard imaging methods.^6,15,16 Other imaging modalities include contrast-enhanced fluoroscopy which can detect esophageal dilation, as well as scintigraphy and video-fluorography which are useful in esophageal motility assessment. ²³ When assessing motility issues in individuals with SSc, especially in those with extensive esophageal involvement, manometry is a crucial tool.^3,4,8

Emerging Therapies and Prognosis

Emerging therapies for managing GI complications in SSc focus on both motility and vascular dysfunction. Prokinetics such as metoclopramide, erythromycin, ² prucalopride, and octreotide have demonstrated effectiveness in alleviating symptoms of gastroparesis and small bowel dysmotility. Therefore, these agents improve symptoms such as bloating, constipation, and nausea. ²⁴ Prokinetic medications used to treat esophageal dysmotility are also the foundation for gastric dysmotility treatment. Gastric per-oral endoscopic pyloromyotomy, a novel unique treatment approach, may improve therapeutic outcomes for individuals with SSc who have not responded to conventional medicine. ² Furthermore, the potential role of immunomodulatory treatments, including intravenous immunoglobulin, is being investigated. This is especially useful for individuals who have anti-muscarinic-3 receptor antibodies and severe, unresponsive GI symptoms. ²⁴

Depending on the degree and severity of organ involvement, patients with GI involvement in SSc have different prognoses. Although GAVE hemorrhage can be controlled with treatments like APC and RFA, GI problems are chronic and recurrent, requiring long-term care and monitoring. When extensive, GI involvement can significantly impact quality of life, especially when combined with malnutrition or ongoing bleeding.^6,7,15

The case report is about a 69-year-old person who has SSc and recently had GI bleeding. The bleeding was caused by 2 vascular complications of the illness: GAVE and rectal telangiectasia. The report discusses how the patient was treated and highlights that using APC to manage bleeding from these vascular lesions was effective.

The report also states that GI bleeding in SSc may be attributed to other conditions such as esophagitis, gastric ulcers, colon angiodysplasia, and colorectal cancer. However, none of these conditions were found in this particular case. Instead, the bleeding was confirmed to be due to vascular issues. This type of diagnosis, which focuses on vascular problems like GAVE and telangiectasia, particularly for SSc patients with chronic illness, is highly supported by the literature.^{1,5,6,7,12,15}

APC is the main treatment for vascular lesions associated with SSc, such as GAVE and rectal telangiectasia.^17,18,24,25 APC is effective in controlling bleeding by cauterizing abnormal blood vessels during endoscopic therapy. Research has shown that APC is successful in treating bleeding from GAVE, with success rates varying from 40% to 100%. ¹⁷ However, recurrence is common, requiring additional endoscopies.^17,18 In this specific case, the patient responded well to APC, and her hemoglobin levels returned to normal after the procedure, showing the effectiveness of APC in managing sudden bleeding.

The positive outcome of using APC in this patient with no complications aligns with results from studies that have used APC to treat GAVE and GI telangiectasia in SSc patients.^17,18,24,25 Even though GAVE did not reappear at discharge in this case, it is a commonly recognized challenge. Studies indicate that a percentage ranging from 10% to 78.9% of patients may experience a recurrence after APC.^17,18 This emphasizes the importance of consistent monitoring and potential additional treatments in the long-term follow-up care plan for this individual.

The typical result of treating GAVE and telangiectasia with APC includes resolving melena and rectal bleeding, as well as normalizing hemoglobin levels. The lack of continued bleeding posttreatment shows successful hemostasis, and the patient being discharged in stable condition demonstrates the safety and effectiveness of APC in this particular situation. The patient must maintain regular contact with gastroenterology and rheumatology, as the return of GAVE and telangiectasia, especially with SSc. The instance highlights how identifying and treating early through endoscopy is crucial in preventing continuous blood loss and complications such as severe anemia.

Conclusion

GI involvement in SSc poses significant challenges, as demonstrated by conditions such as GAVE and rectal telangiectasia which leads to chronic GI bleeding severely impacting patient outcomes. As evidenced by the literature and the case report, the identification of GAVE and telangiectasia as potential sources of GI bleeding in patients with SSc is of utmost importance. Although endoscopic procedures such as APC have been shown to be successful in management of bleeding, the case reinforces the need for vigilant long-term monitoring to prevent recurrence. The integration of therapeutic and supportive treatments, early identification, and tailored care are essential in addressing the intricate problems associated with GI involvement in SSc. Advancements in endoscopic techniques, pharmacological therapies, and a better understanding of the disease pathophysiology provide hope for reducing recurrence rates and improving long-term outcomes in patients suffering from these complex vascular lesions.