Faculty of pharmaceutical sciences, Mewar University Chittorgarh Rajasthan, 312901.
Immunocompromised patients with peptic ulcers pose special challenges in diagnosis, treatment, and management. This review discusses the intricate relationship between immunosuppression and peptic ulcer disease, emphasizing the risk and severity of ulcers in this group of patients. The abstract reviews different states of immunocompromised conditions, such as organ transplant recipients, HIV/AIDS patients, chemotherapy patients, and those on long-term corticosteroid therapy. It explains how these conditions disrupt the usual protective mechanisms of the gastrointestinal tract to make it more susceptible to ulcer development and complications. The review covers the multi-factorial etiology of peptic ulcers in immunocompromised hosts, including Helicobacter pylori infection, drug-induced mucosal damage, and stress-induced mucosal damage. It highlights the frequently atypical presentation of ulcers in this group, which may result in delayed diagnosis and increased morbidity. The abstract presents the diagnostic dilemmas, such as the diminished reliability of conventional tests for the detection of H. pylori in immunosuppressed patients and the requirement for more forceful endoscopic investigation. Additionally, the review discusses the intricacies of the management of peptic ulcers in immunocompromised patients. It speaks about the requirement for individualized treatment plans, taking into account the modified pharmacokinetics and possible drug interactions in such patients. The abstract emphasizes the need to balance optimal ulcer cure with control of the underlying immunosuppressive condition. It also mentions increased susceptibility to complications of bleeding, perforation, and recurrence in such patients and thus the need for closer observation and follow-up. The review reviews existing modalities of treatment such as proton pump inhibitors, H. pylori eradication therapy with antibiotics, and cytoprotective drugs. It also discusses new treatments and preventive therapies directed towards immunocompromised patients. The abstract summarizes by stating areas that need further work in knowledge gap and areas that future research might explore to benefit the difficult-to-treat patient group. It is a review of worth in informing clinicians in charge of taking care of peptic ulcers in immunocompromised individuals, stressing on multidisciplinary management and individually tailored treatment methods.
Peptic ulcers (PUs) are common gastrointestinal lesions of the duodenum or stomach resulting from an imbalance between offending forces (e.g., pepsin and gastric acid) and defense mechanisms (e.g., mucus and bicarbonate). Though common in the general population, their incidence and clinical presentation are highly variable in immunocompromised patients. Immunocompromised patients, who are at increased risk for infection and are usually dependent on pharmacologic agents that suppress immunity, are faced with a distinct set of problems in the diagnosis, treatment, and management of peptic ulcers. These problems are compounded by many factors, including skewed immune responses, drug interactions with immunosuppressive drugs, and susceptibility to opportunistic infections. These problems need to be understood to better manage PUs in immunocompromised patients. [1] The immunocompromised state represents a generalized term for conditions including HIV/AIDS, organ transplant, cancer, and treatment with immunosuppressive therapy for autoimmune disease. These conditions and therapies used to treat them put patients at risk for the development of peptic ulcers. For example, transplant patients on corticosteroids and calcineurin inhibitors (e.g., tacrolimus or cyclosporine) are significantly more likely to develop ulcers than the general population. In these patients, immunosuppressive drugs suppress the immune system but also stimulate gastric acid secretion, thus enhancing ulcer formation. Indeed, studies show that–20-30% of organ transplant recipients develop peptic ulcers, particularly those on triple-drug immunosuppressive therapy. [2] Similarly, HIV/AIDS patients are also a high-risk group for peptic ulcer disease. Chronic immunosuppression in these patients places them at risk for a variety of GI complications, including ulcers. The etiology of peptic Ulcers in HIV-positive individuals are multifactorial, involving direct viral action on the GI tract and opportunistic infections like Candida or cytomegalovirus (CMV), which can result in the formation of ulcers. Also, antiretroviral therapy (ART), in the form of medications like protease inhibitors, can be a causative agent of GI complications, thus making the management of PUs in these individuals complex. It has been seen in research that 15-20% of HIV patients are likely to develop ulcers, more in the patients with more severe disease or those with uncontrolled viral loads. [3] Peptic ulcer disease in immunocompromised patients has a complex pathophysiology, which is quite different from immunocompetent individuals. Peptic ulcers in the general population are primarily due to Helicobacter pylori infection. However, in immunocompromised individuals, the immune system's function to eliminate H. pylori may be impaired, which results in chronic infection and increased risk of ulceration. In these individuals, the administration of corticosteroids and other immunosuppressive medications also prevents mucosal defense mechanisms like prostaglandin synthesis, which is essential for healing ulcers. Also, medications like nonsteroidal anti-inflammatory drugs (NSAIDs), which are used frequently to treat pain in immunocompromised individuals, predispose to ulceration by preventing prostaglandin synthesis and loss of protective mucosal barrier. [4] The peptic ulcers in immunocompromised individuals also have some unusual challenges in diagnosis. The patients present with unusual symptoms of ulceration due to their blunted inflammatory response, which hides common presentations, like epigastric pain, nausea, and vomiting. Thus, ulcers may go undetected for longer periods or be misdiagnosed as other conditions. Also, in these patients, prevention of infection with broad-spectrum antibiotics and antifungals may alter or mask common manifestations of H. pylori infection, thereby making diagnosis harder. Diagnostic tests like H. pylori stool antigen test, urease breath tests, or endoscopy may be less sensitive in immunocompromised hosts due to alterations in immune responses as well as interference from drugs. This necessitates stricter and careful diagnostic evaluation. [5] Therapeutically, treatment of peptic ulcers in immunocompromised hosts needs to strike a balance among several factors. Conventional treatments, such as proton pump inhibitors (PPIs) and antibiotics, for the eradication of H. pylori work well in non-immunocompromised individuals. In immunocompromised individuals, however, these treatments may need to be adjusted due to an alteration in pharmacokinetics and potential drug-drug interactions with immunosuppressant medications. For instance, PPIs, which are commonly employed to reduce gastric acid secretion and enhance healing of ulcers, may interfere with the absorption of other essential drugs like tacrolimus, a central immunosuppressive agent in organ recipients. Second, while eradication of H. pylori continues to be a vital component of ulcer treatment, choice of antibiotics will occasionally need to take into account increasing antibiotic resistance in the context of more susceptible, immunocompromised individuals. [6] One of the most worrying issues in treating peptic ulcers in immunocompromised hosts is the risk of opportunistic infections, which may be facilitated by the use of PPIs and antibiotics. These medications can alter gastric pH, favoring growth of pathogens like Candida spp. and Clostridium difficile, that are particularly risky in immunocompromised hosts. Hence, it is extremely important to place such patients in close follow-up for secondary infection and modulate treatment strategies accordingly. In addition, the possibility of impaired tissue healing and repair in such patients increases the chances of complications such as ulcer perforation, hemorrhage, or gastric outlet obstruction and requires careful follow-up and even surgery. [7] Besides pharmacologic treatment, non-pharmacologic treatments also might have some role in treating peptic ulcer in immunocompromised subjects. Dietary measures, cessation of smoking, reduction of stress, etc., are required in patients with peptic ulcers. Such measures may, however, prove challenging in immunocompromised subjects who have several underlying conditions and active medical therapy. Thus, handling such patients will involve multiple-modal treatment strategies provided by gastroenterologists, infectiologists, and transplant hepatologists in a coordinated effort so as to offer maximum care to obtain the desired outcomes. [8] Overall, treating peptic ulcer in immunocompromised hosts is a distinct challenge from presentation to management. Such subjects risk ulcer development with the underlying condition and treatment disrupting their immune capability. Standard interventions in peptic ulcer might be needed to change in such populations, and high priority needs to be assigned for watching over their pharmacological associations and complications consequent to the disease as well as the treatment. Further, there is a need for intensified research in diagnosing the pathology, designing therapeutic regimens, and enhancing the outcomes of immunocompromised subjects with a high-risk background. [9]
Pathophysiology of Peptic Ulcers in Immunocompromised Patients
Peptic ulcers (PUs) are defined as mucosal lesions of the stomach or duodenum that result from an imbalance between injurious and protective forces in the gastric environment. In immunocompromised individuals, this pathophysiological equilibrium is disrupted further because of changes in immune function, mucosal integrity, and heightened susceptibility to infection, all of which contribute to the causation and worsening of peptic ulcers. Immunocompromised patients, due to diseases such as HIV/AIDS, organ transplantation, or cancer, are at high risk of developing ulcers and more complex clinical courses, such as delayed healing and secondary infections. [1]
One of the major mechanisms involved in peptic ulcer development is excess secretion of gastric acid, which results in damage to the mucosal barrier. In immunocompromised hosts, the use of immunosuppressive agents, such as corticosteroids, calcineurin inhibitors, and other drugs utilized in organ transplants or autoimmune diseases, increases this risk. Although vital in suppressing the underlying disorders, these agents alter mucosal protective mechanisms through interference with the generation of prostaglandins, which are responsible for sustaining gastric mucosal integrity. Low levels of prostaglandins cause mucus and bicarbonate secretion, which shield the lining of the stomach from the corrosive action of acid and pepsin. [4] In addition, the ability of the immune system of immunocompromised patients to defend against infections is impaired; therefore, they are more susceptible to infections that have the potential to cause ulcers. Helicobacter pylori (H. pylori), the most prevalent bacterium in peptic ulcer disease among immunocompetent patients, is also a major cause in immunocompromised patients, although their immune response might be weaker in eliminating the infection. Chronic infection with H. pylori in the gastric mucosa results in a cascade of inflammatory reactions that culminate in disruption of the mucosal barrier. In immunocompromised patients, the infection can take longer and become more difficult to clear, resulting in more severe and refractory ulcers. Along with H. pylori, opportunistic pathogens like Cytomegalovirus (CMV), fungi like Candida, and viral infections complicate ulceration in immunocompromised patients. [8] Medication-induced immunosuppression, as well as diseases such as HIV/AIDS, also cause the body's healing process to fail due to ulcers. Under normal circumstances, the immune system plays a vital role in tissue repair and regeneration following injury. However, in immunocompromised hosts, repair is slowed or impaired through decreased inflammatory responses and defective cell-mediated immunity. For example, diminished T-cell function in HIV/AIDS patients and extensive use of immunosuppressive therapy in transplant recipients prevent natural gastric mucosal healing. This leads to the persistence of ulcers, a greater risk of complications, such as perforation or bleeding, and an extended disease course. [10] In addition, changes in the gut microbiota of immunocompromised hosts may also be a factor in peptic ulcer pathogenesis. Evidence suggests that equilibrium of microbial populations within the GI tract plays a crucial role in ensuring mucosal integrity and protecting against infection. In immunocompromised individuals, antibiotic prophylaxis against infection combined with immunosuppressive drugs can alter the gut microbiota and cause dysbiosis. This dysbiosis can foster the overgrowth of pathogenic microorganisms, such as opportunistic infections caused by Candida spp. and Clostridium difficile, which in turn can cause further damage to the mucosal lining and exacerbate ulceration. [6]
Risk Factors and Causes
Peptic ulcers are ulcers that occur on the lining of the stomach, small intestine, or esophagus as a result of erosion of the mucosal layer. In immunocompromised individuals, the ulcers may be more common and severe as a result of immune system changes, exposure to various pathogens, and use of specific drugs. Below are the primary risk factors and etiology of peptic ulcers in these patients.
Use of Immunosuppressive Drugs
Immunocompromised individuals tend to need immunosuppressive medications such as corticosteroids, cyclosporine, methotrexate, and biologics (e.g., tumor necrosis factor inhibitors). These drugs have the potential to suppress the immune system and contribute to an increased risk of infections, including Helicobacter pylori infection, a major cause of peptic ulcers. Moreover, corticosteroids may suppress the formation of protective gastric mucus and inhibit prostaglandin synthesis, which enhances gastric acid secretion and renders the mucosa more vulnerable to damage. [11]
Helicobacter pylori Infection
Helicobacter pylori is a gram-negative bacillus that inhabits the stomach and is a proven etiology of peptic ulcers. In immunocompromised hosts, the host response to H. pylori can be deficient, resulting in chronic infection and enhanced potential for ulcer development. The bacterium's capacity to thrive in the stomach's acidic environment, as well as its production of urease, which can counteract stomach acid, plays a role in its virulence. Immunosuppressive therapy also diminishes the host's capacity to respond to this infection, further enhancing the potential for peptic ulcer disease. [12]
Stress and Physical Trauma
Stress-induced mucosal injury is another important cause of peptic ulcers in immunocompromised hosts, particularly in the intensive care unit. Trauma, surgery, and sepsis elevate gastric acid production, while at the same time impairing the protective capability of the stomach. In the case of immunocompromised patients, this imbalance can produce an ulcer. Additionally, such people might be more susceptible to the action of stress because their immune defense mechanisms are compromised. [13]
Increased Gastric Acid Secretion
In immunocompromised patients, especially those on prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, gastric acid secretion may be increased. NSAIDs and corticosteroids both inhibit the release of prostaglandins, which are responsible for protecting the gastric mucosal barrier. The decrease in mucosal defense that results leaves the lining of the stomach more susceptible to damage by stomach acid. [14] Viral Infections Some viral infections, like cytomegalovirus (CMV), predispose immunocompromised individuals to peptic ulcers. CMV has been reported to cause ulcerations in the gastrointestinal tract, such as in the stomach and small intestine. This is particularly prevalent in those who are on immunosuppressive therapy for organ transplantation or HIV/AIDS. CMV infection can result in direct mucosal damage and inflammation, which promotes ulcer formation. [15]
Gastric Ischemia and Compromised Blood Flow
Patients who are immunocompromised, especially with diseases such as diabetes mellitus or extensive surgical procedures or intensive care, have a higher chance of gastric ischemia, an interruption of blood flow to the stomach lining. This diminished blood flow worsens the ability of the stomach to heal following injury and also predisposes the stomach to developing ulcers. Furthermore, medications used to manage these conditions may increase the risk of ulcer development. [16]
Clinical Presentation and Diagnosis
Immunocompromised patients with peptic ulcers may have clinical presentation identical to that of immunocompetent hosts, but underlying immune deficiency may contribute to more severe or atypical presentations. Diagnosis may be difficult based on unusual presentation or concomitant comorbid diseases. The following is a summary of clinical presentation and diagnostic strategy for peptic ulcers in immunocompromised individuals.
Clinical Presentation
Abdominal Pain and Dyspepsia
Immunosupromised patients often present with their most frequent sign of peptic ulcers: abdominal pain in the form of a burning, gnawing sensation in the upper abdomen. The pain has an intermittent characteristic, typically recurring after meals and with stress episodes. But in immunocompromised individuals, the characteristically localized pattern of pain can be diffuse or diffuse, and the patient can fail to have the characteristic symptom of pain relief after meals seen in more classic cases. For some patients, there can be associated bloating, nausea, or vomiting. [17]
Gastrointestinal Bleeding
Gastrointestinal bleeding is a more frequent and more serious complication of peptic ulcers in immunocompromised individuals. It may be in the form of hematemesis (vomiting blood), melena (black tarry stools), or even frank red rectal bleeding. The risk of bleeding is increased in patients on anticoagulants, in Helicobacter pylori infection, or in a history of trauma or surgery. Hemorrhage can be the initial symptom in certain immunocompromised patients, particularly those with impaired capacity to mount a proper inflammatory response. [18] Perforation and Peritonitis Peptic ulcer perforation, although less frequent, can happen in immunocompromised individuals and is characterized by acute, severe abdominal pain and peritonitis signs like guarding, rigidity, and rebound tenderness. Perforation is a life-threatening situation and is more probable in patients who have chronic or untreated ulcers. The compromised infection-fighting capacity of immunocompromised patients can lead to delayed healing and susceptibility to perforation. [19]
Atypical or Asymptomatic Presentation
Peptic ulcers can be asymptomatic or have very mild symptoms in certain immunocompromised individuals, especially the elderly and the severely immunosuppressed. They might experience mild pain or loss of appetite. Diagnosis becomes challenging in such cases, and ulcers are found during investigations for other reasons or in the setting of complications such as bleeding or perforation. [20]
Diagnosis
Endoscopy (Esophagogastroduodenoscopy - EGD)
Endoscopy is the standard for the diagnosis of peptic ulcers in both immunocompetent and immunocompromised patients. It provides direct visualization of the ulcer, the degree of injury, and the presence of complications like bleeding or perforation. In immunocompromised individuals, endoscopy is especially useful since it can detect ulcers that are not clinically apparent. Also, biopsies can be obtained during endoscopy to diagnose Helicobacter pylori infection, malignancy, or other conditions causing ulceration, like cytomegalovirus (CMV) in case of extensive immunosuppression. [21]
Helicobacter pylori Testing
Helicobacter pylori infection should be tested for in the diagnosis of peptic ulcers, particularly in immunocompromised patients with a higher risk of chronic infection. There are various methods, such as urea breath tests, stool antigen tests, and biopsy-based techniques during endoscopy. But in immunocompromised patients, particularly those on antibiotics or proton pump inhibitors (PPIs), non-invasive tests like the urea breath test can be less sensitive. Biopsy during endoscopy is still a more reliable option in such patients. [22]
Radiological Imaging
Although endoscopy is the first-line diagnostic method, in the event that endoscopy is unavailable or contraindicated, radiology like a contrast-enhanced upper GI series can be employed to image ulcers and their complications like perforation or gastric outlet obstruction. Radiology is however less sensitive than endoscopy and does not permit biopsy. [23] CMV PCR and Histopathology In immunocompromised individuals with suspected viral etiology of ulcers like CMV, PCR may be employed to identify CMV DNA in gastric biopsies. Histopathology can also identify characteristic cell inclusions in cells infected with CMV, again supporting the diagnosis. Ulcers due to CMV tend to be larger, irregular, and may be seen with involvement of deeper layers of tissue. [24]
Laboratory Tests
Laboratory investigations like complete blood counts (CBC) and liver function tests can be helpful in determining the overall health status of the patient as well as diagnosing complications such as bleeding or infection. Low hemoglobin values in patients with extensive bleeding suggest a bleeding ulcer. Patients with chronic ulcers or those having H. pylori infection could have increased levels of inflammation markers, e.g., C-reactive protein (CRP). [25]
Challenges in Management
The management of peptic ulcers in immunocompromised patients has several issues because of impaired immune responses, heightened susceptibility to infection, and possible complications due to comorbid conditions. Complications are also worsened by drug interactions and delayed healing. Among the major issues is an increased prevalence of Helicobacter pylori (H. pylori) infection and problematic eradication in immunocompromised patients. Immunosuppressed patients, like those with organ transplants or autoimmune conditions, also face impaired infection-clearing abilities, making the usual antibiotic treatment less effective. The development of resistance to frequently prescribed antibiotics like clarithromycin and metronidazole complicates therapy further, requiring alternative therapies or combination treatments with higher side effects and toxicity potentials. [26] Another point of concern is the higher incidence of NSAID ulcers. Numerous immunocompromised patients, particularly those with rheumatoid arthritis or other chronic diseases, need prolonged NSAID therapy. NSAIDs, however, cause gastric mucosal injury by suppressing prostaglandin synthesis, which is important in the maintenance of gastric lining integrity. Proton pump inhibitors (PPIs) or misoprostol as gastroprotective drugs are routine, but long-term use of PPIs has been linked with side effects like osteoporosis, Clostridium difficile infections, and renal disease, a balance between prevention of ulcers and side effects. [27] Delayed healing of ulcers is also a significant issue since immunocompromised individuals usually have poor tissue regeneration and repair. Diseases such as diabetes mellitus, HIV/AIDS, and post-transplant immunosuppression also inhibit angiogenesis and fibroblast activity, delaying ulcer healing. Corticosteroids, which are also frequently used in these patients, further inhibit inflammatory reactions, causing chronic ulceration and risk of perforation or hemorrhage. This requires strict monitoring and patient-specific treatment approaches to maximize healing with minimal side effects. [28] In addition, the likelihood of fulminant complications beyond bleeding and perforation is much greater in immunocompromised patients. These individuals tend to have associated coagulopathies, thrombocytopenia, or vascular susceptibility, and thus ulcer hemorrhage is more resistant to control. Endoscopic measures, including hemostatic clips or thermal coagulation, become more frequently necessary in some cases, with the requirement for surgical treatment in others. Nevertheless, operation results in immunocompromised individuals tend to be worse because of impaired wound healing and enhanced susceptibility to infection. [29]
Management Strategies
Treatment of peptic ulcers in immunocompromised individuals involves a multifaceted strategy with an emphasis on treating the underlying cause, promoting ulcer healing, and averting complications. The treatment options include specific pharmacological treatment, control of infection, life-style changes, and regular follow-up to assess response to treatment. Acid suppression therapy with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) forms a major part of treatment. PPIs, including omeprazole and pantoprazole, are the first-line drugs because of their strong acid suppression, which facilitates ulcer healing and minimizes the risk of bleeding. Long-term PPI therapy should be closely monitored in immunocompromised patients, though, because it can enhance susceptibility to Clostridium difficile infection and pneumonia. [30] Eradication of Helicobacter pylori (H. pylori) is indicated in patients with proven infection. The standard triple therapy of a PPI, clarithromycin, and amoxicillin or metronidazole is usually applied. Nevertheless, in the context of the widespread prevalence of antibiotic resistance among immunocompromised patients, different regimens including quadruple therapy (bismuth-containing) or sequential therapy can be used. In addition, evaluation of the efficacy of treatment by means of urea breath tests or stool antigen tests is advised upon completion of therapy. [31] For individuals needing long-term corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs), co-treatment with PPIs or misoprostol is recommended to avoid ulcer development. In transplant patients and autoimmune disease patients, reducing corticosteroid use or substituting with steroid-sparing immunosuppressants, e.g., biologics, may decrease the risk of mucosal damage caused by NSAIDs. [32] Careful consideration for opportunistic infection, including cytomegalovirus (CMV) or fungal ulcers, that can be a mimic for peptic ulcers in immunocompromised patients is also part of management. Biopsy and histopathological verification in patients with suspected viral or fungal ulcers is crucial. Specific antiviral therapy (e.g., ganciclovir for CMV) or antifungal medication (e.g., fluconazole for esophageal Candida infection) should be started according to the pathogen detected. [33] Lifestyle changes and nutritional support are important in the management of ulcers. Patients must be instructed to abstain from alcohol, smoking, and irritating foods. In instances where oral intake is impaired because of extensive ulceration or secondary conditions such as mucositis, enteral nutrition can be used to provide sufficient caloric supply and promote mucosal healing. [34] Endoscopic surveillance is required for high-risk patients, especially those with recurrent ulcers, refractory symptoms despite treatment, or a history of ulcer complications like bleeding or perforation. Endoscopy facilitates early identification of refractory ulcers, malignancies, or other complications that might need surgery. [35] Last but not least, compliance with therapy is key to successful treatment. With the polypharmacy that is often encountered in immunocompromised patients, treatment regimens should be well tolerated and not interfere with other necessary medications. Patient education and follow-up improve compliance and maximize treatment results. [36]
Preventive Strategies
Prevention of peptic ulcers in immunocompromised patients is important because they are at high risk of developing ulceration, delayed healing, and complications. Prevention involves decreasing acid secretion, avoiding ulcerogenic drugs, eradicating Helicobacter pylori (H. pylori), and modifying lifestyle factors leading to ulcer formation. Acid suppression therapy is the cornerstone in prevention of peptic ulcers in high-risk patients. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are used to protect the gastric mucosa against excessive acid exposure. PPIs, including omeprazole and esomeprazole, are chosen due to their greater efficacy in the prevention of stress-related mucosal injury, especially in transplant patients and those on high-dose corticosteroids or NSAIDs. [31] Eradication of H. pylori is an important strategy in preventing recurrence of ulcers. Immunocompromised individuals, particularly those with HIV/AIDS or receiving chemotherapy, are at high risk of chronic H. pylori infection because of compromised immune mechanisms. Screening at regular intervals and early eradication with combination therapy, including quadruple therapy (bismuth, PPI, tetracycline, and metronidazole), is advocated to minimize ulcer risk and complication. For patients needing long-term NSAIDs or corticosteroids, prevention involves co-administration of gastroprotective agents like PPIs or misoprostol. Furthermore, the use of selective COX-2 inhibitors rather than conventional NSAIDs can reduce the risk of gastrointestinal mucosal injury. In transplant patients and autoimmune disease patients, treatment of immunosuppressive therapy by decreasing corticosteroid doses or changing to steroid-sparing drugs like biologics can also help avert ulcer development. [32] Another preventative factor is the identification and management of opportunistic infections that help in ulcer development. In immunocompromised hosts, ulcers can be produced by viral (e.g., cytomegalovirus) or fungal (e.g., Candida) infections instead of H. pylori or NSAIDs. Prophylactic surveillance, prompt endoscopic examination, and specific antimicrobial treatment of these infections avoid ulcer complications. [33] Nutritional measures and lifestyle adjustments also contribute to the prevention of ulcers. The avoidance of alcohol, smoking, and food irritants like spicy foods minimizes mucosal irritation. Also, provision of sufficient protein and micronutrient supplementation (e.g., zinc and vitamin C) promotes mucosal repair and enhances gastric protection, especially in patients with malnutrition or chronic diseases. [34]
Continuous monitoring and early treatment in at-risk patients prevent ulcer complications. Immunosuppressed patients, particularly those with a history of ulcers, require regular endoscopic assessment to identify early evidence of mucosal damage. Therapy tailoring on endoscopic outcome, and patient counseling regarding compliance to drugs and diet changes, radically decreases the recurrence and incidence of ulcers. [35]
Recent Advances and Future Perspectives
The treatment of peptic ulcers in immunocompromised individuals has changed with advances in diagnostic technologies, specific therapies, and individualized treatment strategies. Current studies aim to enhance ulcer healing, maximize treatment regimens, and minimize complications using new pharmacological agents, microbiome-targeted therapies, and advanced endoscopic methods.One of the important developments is the creation of potassium-competitive acid blockers (P-CABs) like vonoprazan. In contrast to older proton pump inhibitors (PPIs), P-CABs offer quicker, stronger, and more enduring acid suppression, which is very effective against preventing and treating peptic ulcers, particularly in immunocompromised hosts who need long-term acid suppression. [37] Another area of research with much promise is the application of probiotics and modulation of gut microbiota for ulcer treatment. Dysbiosis in immunocompromised patients may worsen gastric mucosal injury and impair healing of ulcers. Research indicates that probiotics like Lactobacillus and Bifidobacterium species restore balance in gut microbiota, increase mucosal protection, and increase rates of H. pylori eradication when prescribed as an adjunct to regular therapy. [38] Improved techniques in H. pylori eradication have also enhanced treatment outcomes for immunocompromised hosts. As antibiotic resistance grows, new treatment regimens, including rifabutin-containing triple therapy and high-dose amoxicillin dual therapy with PPIs, have been beneficial. Next-generation sequencing (NGS) and molecular testing also enable personalized treatment of H. pylori according to resistance patterns, providing a greater rate of eradication.[39] Endoscopic technology has improved diagnosis and treatment of peptic ulcers and their complications in the early stages. Procedures like endoscopic submucosal dissection (ESD) and over-the-scope clips (OTSC) achieve improved hemostasis in the event of massive ulcer bleeding. AI-based endoscopy also enhances the sensitivity of ulcer diagnosis and differentiation from malignancy, facilitating early treatment and minimizing complications. [40] The future directions in ulcer treatment involve regenerative medicine strategies, including stem cell therapy and tissue engineering. Preclinical research indicates that mesenchymal stem cells (MSCs) enhance gastric mucosal repair by minimizing inflammation and maximizing tissue repair. Such therapies have promise for the treatment of refractory ulcers in immunocompromised hosts with compromised healing potential. [41] Another area of promise is the use of biomarkers and genetic profiling to develop personalized medicine approaches. Identification of patient-specific risk factors, such as genetic predisposition to ulcer development and drug metabolism differences, may allow for customization of treatment regimens and enhancement of therapeutic effect with reductions in adverse effects in immunocompromised hosts. [42]
CONCLUSION
Immunocompromised patients with peptic ulcers pose a complicated clinical problem with compromised mucosal defense mechanisms, delayed healing, and increased risk of complications like perforation, bleeding, and secondary infection. Such patients, such as those with HIV/AIDS, malignancies, autoimmune diseases, or organ transplant recipients, need a multidisciplinary and specialized approach to diagnosis, management, and prevention. The synergistic interaction of multiple risk factors, such as Helicobacter pylori infection, long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and opportunistic infections, also increases the complexity of disease progression and treatment planning. Resolution of these issues demands a customized, evidence-based strategy that combines pharmacological management, lifestyle intervention, and ongoing surveillance in order to best maximize patient outcomes. Acid suppression therapy is still the mainstay of ulcer treatment in immunocompromised patients, with proton pump inhibitors (PPIs) as first-line therapy. Long-term PPI therapy, though, has also raised issues about adverse events like heightened vulnerability to gastrointestinal infection, osteoporosis, and renal impairment. The development of potassium-competitive acid blockers (P-CABs) presents a promising option with improved acid inhibition, quick onset, and potentially less side effects. Moreover, eradication of H. pylori continues to play an essential role in prevention and management of ulcers, with progressive antibiotic resistance requiring new therapeutic strategies like quadruple therapy, high-dose amoxicillin-based dual therapy, and rifabutin-based regimens based on individual resistance patterns. Molecular diagnostic advances, including next-generation sequencing (NGS), have dramatically enhanced the precision of H. pylori detection and resistance testing, allowing for personalized treatment regimens. The contribution of gut microbiota to peptic ulcer pathogenesis is a developing topic of interest, especially in immunocompromised individuals, where dysbiosis can contribute to gastric mucosal damage. Probiotic supplementation with Lactobacillus and Bifidobacterium strains has been found to have potential in augmenting mucosal defense, enhancing H. pylori eradication, and preventing recurrent ulcers. Prospective investigation into microbiome-targeted treatment, such as fecal microbiota transplantation (FMT), has the potential to provide new therapeutic options in refractory and recurrently infected patients. Technical developments in endoscopy have greatly improved peptic ulcer diagnosis and treatment of immunocompromised individuals. The incorporation of artificial intelligence (AI) into endoscopic imaging has improved early ulcers detection, recognition of high-risk lesions, and discrimination from malignancies, thus allowing for immediate and accurate interventions. New endoscopic therapeutic modalities including endoscopic submucosal dissection (ESD), over-the-scope clips (OTSC), and hemostatic powders have improved significantly hemostasis in ulcer patients with severe bleeding, minimizing the necessity for surgical treatment. Additionally, regenerative medicine strategies such as stem cell therapy have the potential to enhance mucosal healing among patients with refractory ulcers and dysfunctional mechanisms of tissue repair. Preventive measures are particularly important in reducing peptic ulcers' occurrence and recurrence in immunocompromised individuals. Risk stratification, regular endoscopic monitoring, and lifestyle change like smoking abstinence, reduction of alcohol use, and eating habits modification are vital in the prevention of ulcers. Medication management, such as the use of COX-2 inhibitors rather than conventional NSAIDs and steroid-sparing immunosuppressants, can reduce ulcerogenic risks. Multidisciplinary teamwork between gastroenterologists, infectious disease specialists, transplant physicians, and dietitians is also crucial to providing holistic patient care and reducing complications. In the future, peptic ulcer treatment in immunocompromised patients will be shaped by advances in precision medicine, AI-based diagnostics, and new therapeutic agents. Individualized treatment regimens using genetic profiling, biomarker identification, and pharmacogenomics will allow for targeted therapy with enhanced efficacy and diminished side effects. Clinical decision-support systems powered by AI will complement early detection, risk evaluation, and treatment optimization, laying the foundation for more effective and personalized patient management. In summary, although considerable progress has been made in the comprehension and management of peptic ulcers in immunocompromised individuals, sustained research and innovation are critical to solving the unresolved issues. An integrated and multi-disciplinary approach that includes novel pharmacological therapies, microbiome modulation, endoscopic innovation, and personalized medicine will be fundamental to enhancing patient outcomes and lessening the peptic ulcer disease burden in this susceptible population.
REFERENCES
Pankaj Chasta*, Akash Ahmad, Reviewing the Peptic Ulcers in Immunocompromised Patients: Challenges and Management Strategies, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 3, 2915-2927. https://doi.org/10.5281/zenodo.15103588
10.5281/zenodo.15103588
