**1. Introduction**

176 Immunodeficiency

2004;39(4):588-90.

2002;16(4):895-914,

[92] Kauffman CA. Zygomycosis: reemergence of an old pathogen. *Clin Infect Dis*. 15

[93] Gonzalez CE, Rinaldi MG, Sugar AM. Zygomycosis. *Infect Dis Clin North Am*.

Immunodeficiency (or immune deficiency) is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Most cases of immunodeficiency are acquired (secondary) but some people are born with defects in their immune system (Primary) immunodeficiency.

The following conditions and diseases that are associated with primary immunodeficiency disorder include, Combined variable immunodeficiency disease, Ataxia-telangiectasia, Chediak-Higashi syndrome, Complement deficiencies, DiGeorge syndrome, Hypogammaglobulinemia, Job syndrome, Leukocyte adhesion defects, Bruton disease, Congenital agammaglobulinemia, Selective deficiency of IgA, Wiscott-Aldrich syndrome etc

As for acquired immunodeficiency, in 2006, UNAIDS and the World Health Organization estimated that approximately 39.5 million people were living with HIV. That year alone, there were 4.3 million new infections, with the majority occurring in sub-Saharan Africa. HIV targets T cells, and in particular, T helper cells, which are critical to fighting infections caused by fungi and parasites. This is why people with advanced, untreated AIDS develop unusual infections such as *Pneumocystis carinii* pneumonia and *Toxoplasmosis gondii*.

Since transplanted organs such as kidneys, hearts, livers, and lungs are foreign bodies, recipients' immune systems must be permanently suppressed to prevent them from attacking and destroying the organs. More than 19,000 transplants are performed in the United States each year. Each month, approximately 3,700 people are added to the U.S. national transplant waiting list, and each day, 77 people receive organ transplants. The breakthrough in transplant technology occurred in 1983 when cyclosporine, a powerful immunosuppressive drug, became licensed. However, even with cyclosporine, transplanted organs typically only last around 10 years before needing to be replaced. Research efforts to

© 2012 Hughes Okafor, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

induce bodies to tolerate transplanted organs without using immunosuppressive drugs are ongoing. But until a breakthrough in understanding immunologic tolerance or a way to grow replacement organs occurs, newly immunocompromised organ-transplant recipients will occur each year.

Pattern of Clinical Presentations in Immunocompromised Patient 179

Immunocompromised patients are prone to various infectious and non infectious disorders. The infectious disease is the commonest presentations of these patients because of the weakening of the patient's immune state. The severity of the infection depends on the degree of the immunosuppression. Some organs like respiratory pathways are more liable to infections in these patients for obvious anatomical reasons; however all organs are at risk of

Also there are various non infectious manifestation in patients with immunosuppression. These may be directly or indirectly related to the degree of immune suppression in the patient. Patients have presented with various degrees of impaired kidney function, liver disease, cardiorespiratory dysfunction, psychosocial, dermatological and neurological

Immunocompromised patients also can present with features not directly related to immunosupression. For example obesity in patients on steroid therapy, and hepatic disease

Clinical presentations in immunocompromised differs among patients. The presentations are determined by the severity of the immunosupression, the severity of the infection and other comorbid condition. Furthermore the organ involved and the type of the associated clinical state play important role in determining the presentation of the patient. There are many uncommon presentations that have been reported in these patients. However poor response to treatment of infection, incomplete recovery from illness, certain types of infections and malignancies are common presentations seen in immunocompromised

The clinical setting is extremely important in recognizing immunosuppression. Immune dysfunction induced by therapeutic intervention will be evident from the history, but immune impairment due to underlying disease may be more difficult to recognize. Inherited immune deficiencies often have characteristic patterns of disease distribution and may be

The various organs/systems in the body have differing impact by the resultant effect of immunosuppression. This results from either the direct impact of the immunosupression or

These manifestations will be discussed according to the impact on various systems and

The primary function of the gastrointestinal tract is digestive, absorption and assimilation of nutrients. It has the largest surface area among all organs. With such large surface area and its close proximity to the external environment it necessitates that it evolved a large compliment of both innate and acquired immune mechanism. The gastrointestinal associated lymphoid tissue constitutes the largest immune compartment in the body. It is

associated with other clinical abnormalities (such as cardiac anomalies).

diseases resulting from the immunosupression.

**2. Gastrointestinal tract in immunocompromised** 

developing infection.

patients.

organs..

disorders that are not directly related to infections.

associated with severe combined immunodeffiency disease.

In addition, cancer chemotherapies typically cause immunosuppression. Since cancer cells are cells that multiply uncontrollably, the goal of cancer therapy is to kill them without killing too many normal cells. Unfortunately, the cells involved in immunity are frequently adversely affected by chemotherapy, thus rendering the patient vulnerable to infections.

Autoimmune disorders are typically treated with immunosuppressive drugs such as corticosteroids, 6-mercaptopurine, and azathioprine to keep the immune system from attacking the body. For example, Crohn's disease is an autoimmune disease in which the immune system attacks the body's gastrointestinal system, causing intense pain, bleeding, and obstructions. Another treatment is infliximab, which stops the body's inflammatory response. But these treatments only alleviate pain and suffering, they don't cure the underlying immune disorder.

Also splenectomy, diabetes mellitus, cancer, increasing age, chronic diseases and strenuous exercise had been associated with various degrees of impairment in immune functions

The immune System`s primary function is to fight off infection. When the immune system is suppressed or dysfunctional the ability to combat infection is reduced. A person who has an immunodeficiency of any kind is said to be immunocompromised. These immunocompromised patients are more vulnerable to infections including infection with organisms that don't normally cause disease. In addition, they are more likely to develop severe and sometimes life-threatening illness following infection.

Many patients admitted into the Medical Unit especially Intensive Care Unit (ICU) have varying degrees of immunosuppression. In some, immunosuppression is easily apparent, especially when caused directly by underlying disease (such as haematological malignancy) or treatment (such as drugs used to prevent organ rejection or as a side effect of cancer chemotherapy). In others, immunosuppression is less apparent and is induced by the underlying disease, for example following traumatic injury or sepsis, or as a response to therapies provided during intensive care such as steroids.

Immunosuppression itself does not cause pathology but does leave the patient prone to infection and other disease conditions. There is no good clinical test to measure the degree of immunosuppression; the clinician must simply maintain a high index of suspicion. The consequences of immune suppression in most patients highlight the importance of infection prevention and control, as well as surveillance measures to ensure that appropriate treatment is implemented safely and quickly. Thus there is need to understand the pattern of clinical presentations of patients with immune dysfunction to avoid delay in making diagnosis and hence intervention.

Immunocompromised patients are prone to various infectious and non infectious disorders. The infectious disease is the commonest presentations of these patients because of the weakening of the patient's immune state. The severity of the infection depends on the degree of the immunosuppression. Some organs like respiratory pathways are more liable to infections in these patients for obvious anatomical reasons; however all organs are at risk of developing infection.

178 Immunodeficiency

infections.

will occur each year.

underlying immune disorder.

induce bodies to tolerate transplanted organs without using immunosuppressive drugs are ongoing. But until a breakthrough in understanding immunologic tolerance or a way to grow replacement organs occurs, newly immunocompromised organ-transplant recipients

In addition, cancer chemotherapies typically cause immunosuppression. Since cancer cells are cells that multiply uncontrollably, the goal of cancer therapy is to kill them without killing too many normal cells. Unfortunately, the cells involved in immunity are frequently adversely affected by chemotherapy, thus rendering the patient vulnerable to

Autoimmune disorders are typically treated with immunosuppressive drugs such as corticosteroids, 6-mercaptopurine, and azathioprine to keep the immune system from attacking the body. For example, Crohn's disease is an autoimmune disease in which the immune system attacks the body's gastrointestinal system, causing intense pain, bleeding, and obstructions. Another treatment is infliximab, which stops the body's inflammatory response. But these treatments only alleviate pain and suffering, they don't cure the

Also splenectomy, diabetes mellitus, cancer, increasing age, chronic diseases and strenuous exercise had been associated with various degrees of impairment in immune functions

The immune System`s primary function is to fight off infection. When the immune system is suppressed or dysfunctional the ability to combat infection is reduced. A person who has an immunodeficiency of any kind is said to be immunocompromised. These immunocompromised patients are more vulnerable to infections including infection with organisms that don't normally cause disease. In addition, they are more likely to develop

Many patients admitted into the Medical Unit especially Intensive Care Unit (ICU) have varying degrees of immunosuppression. In some, immunosuppression is easily apparent, especially when caused directly by underlying disease (such as haematological malignancy) or treatment (such as drugs used to prevent organ rejection or as a side effect of cancer chemotherapy). In others, immunosuppression is less apparent and is induced by the underlying disease, for example following traumatic injury or sepsis, or as a response to

Immunosuppression itself does not cause pathology but does leave the patient prone to infection and other disease conditions. There is no good clinical test to measure the degree of immunosuppression; the clinician must simply maintain a high index of suspicion. The consequences of immune suppression in most patients highlight the importance of infection prevention and control, as well as surveillance measures to ensure that appropriate treatment is implemented safely and quickly. Thus there is need to understand the pattern of clinical presentations of patients with immune dysfunction to avoid delay in making

severe and sometimes life-threatening illness following infection.

therapies provided during intensive care such as steroids.

diagnosis and hence intervention.

Also there are various non infectious manifestation in patients with immunosuppression. These may be directly or indirectly related to the degree of immune suppression in the patient. Patients have presented with various degrees of impaired kidney function, liver disease, cardiorespiratory dysfunction, psychosocial, dermatological and neurological disorders that are not directly related to infections.

Immunocompromised patients also can present with features not directly related to immunosupression. For example obesity in patients on steroid therapy, and hepatic disease associated with severe combined immunodeffiency disease.

Clinical presentations in immunocompromised differs among patients. The presentations are determined by the severity of the immunosupression, the severity of the infection and other comorbid condition. Furthermore the organ involved and the type of the associated clinical state play important role in determining the presentation of the patient. There are many uncommon presentations that have been reported in these patients. However poor response to treatment of infection, incomplete recovery from illness, certain types of infections and malignancies are common presentations seen in immunocompromised patients.

The clinical setting is extremely important in recognizing immunosuppression. Immune dysfunction induced by therapeutic intervention will be evident from the history, but immune impairment due to underlying disease may be more difficult to recognize. Inherited immune deficiencies often have characteristic patterns of disease distribution and may be associated with other clinical abnormalities (such as cardiac anomalies).

The various organs/systems in the body have differing impact by the resultant effect of immunosuppression. This results from either the direct impact of the immunosupression or diseases resulting from the immunosupression.

These manifestations will be discussed according to the impact on various systems and organs..

#### **2. Gastrointestinal tract in immunocompromised**

The primary function of the gastrointestinal tract is digestive, absorption and assimilation of nutrients. It has the largest surface area among all organs. With such large surface area and its close proximity to the external environment it necessitates that it evolved a large compliment of both innate and acquired immune mechanism. The gastrointestinal associated lymphoid tissue constitutes the largest immune compartment in the body. It is estimated that the GIT contains about 60% of the total body lymphocyte. The immune cells in the GIT are organized into distinct anatomic and functional sub compartments..

Pattern of Clinical Presentations in Immunocompromised Patient 181

*Diverticular disease had been reported in immunocompromised patients especially in post transplant patients on immunosuppressive therapy. The clinical presentation varies from asymptomatic to peritonitis. Complicated diverticulitis which was reported in 1.1% of renal transplant patients can* 

*Acute pancreatitis in immunocompromised patients are not common. It has been associated with alcohol ingestion, billiary stones, malignancy, hepatitis B and cytomegalovirus infection. Acute pancreatitis markedly increase the morbidity and mortality associated with immunodeficiency. The* 

*There is increase in prevalence of both common and uncommon gastrointestinal malignancies in patients with immune deficiency. Decreased immune surveillance, continuous mucosa inflammation, gastrointestinal infections, ingestion of carcinogens including medications are some of the factors suspected to be responsible for the heightened prevalence of malignancy in these patients. Also cigarette smoking, sclerosing cholangitis, crohns syndrome and splenectomy had been reported as risk factor for the development of gastrointestinal malignancy in these patients. The gastrointestinal malignancies that have been associated with immunosuppression include Kaposi sarcoma, colorectal carcinoma, post transplant lymphoproliferative lymphoma, gastric mucosa associated lymphoma. The malignancies are initially asymptomatic however acute abdomen from perforation or obstruction and gastrointestinal bleeding are the usual though late* 

The commonly experienced gastrointestinal (digestive) complications; include oral lesions, esophageal lesions, diarrhea, and anorectal diseases (disease that affects the anus and/or rectum). The oral lesions are aphthous ulcer, oral thrush (candidiasis), oral wart, oral hairy

The oesophageal lesions include oesophageal candidiasis, oesopheal herpes simplex, cytomegalovirus, aphthous ulcer, malignancy, and reflux oesophagitis manifesting as

The anorectal lesions which are usually seen in immunocompromised patients with AIDS include herpes simplex infection, gonorhoea, syphilis, anal wart(condylomata) and

Diarhoea is a common clinical presentation in immunocompromised patients independent of the cause. This has been attributed to gastrointestinal infections, malabsorption,

The hepatobilliary system is usually considered part of the digestive system however they have both digestive and non digestive functions. The liver acts as a detoxifier by processing potentially harmful agents into safe chemicals. It is also responsible for metabolism of

dysphagia, odynophagia, and sensation of food sticking in the throat.

**3. Hepato billiary system in immunocompromised** 

glucose, fat and protein. It manufactures and controls the release of bile.

*presents as intestinal perforation, abscess, phlegmon or fistula.* 

*clinical presentation is usually atypical.* 

*presentations.* 

Chlamydia.

medications etc.

leukoplakia, Kaposi sarcoma.

The gastrointestinal tract associated lymphoid tissue, can be divided into three sectors. The first is represented by the pharyngeal tonsils, the appendix, and the large aggregates of nodules known as Peyer patches located at intervals throughout the small intestine. The second sector includes the lymphocytes and plasma cells that populate the basement membrane (lamina propria) of the small intestine, the area of loose connective tissue above the supporting tissue of the mucosal lining extending into the villi. The third sector comprises lymphocytes that lie between the epithelial cells in the mucosa. The interaction between these cells of the lymphatic system and the threatening agent is the basis of defense in the gastrointestinal tract. The gastrointestinal tract also posses other protective measures which include tight epithelial junctions, the digestive enzymes, the acidic gastric fluid, the lysozyme and the high flow of the gastrointestinal fluid.

However the gastrointestinal tract is particularly at risk of infectious and non infectious injuries because of the following reasons – because of their close proximity to the external environment and continuous exposure to myriad of food and other infectious and non infectious antigens, the mucosa is maintained in physiologic inflammatory state characterized by presence of proinflammatory cytokines, marked expression of CCR5 and CXCR4 chemokine receptor that promotes HIV entry into the mucosa cells.

In immunocompromised patients the normal defenses are disrupted, leading to a wide range of clinical and pathogenic consequences. This usually leads to various disease conditions that can be classified into one of several general categories: infections, mucosal injury and ulceration, biliary tract diseases, diverticular disease, pancreatitis, and malignancy

The infections may be bacterial, viral, fungal, or parasitic and may infect one or more gut segments between the mouth and anus. The viral infections that had been reported in these patients include cytomegalovirus, herpes simplex, human papilloma virus, ebstein barr virus and rota virus. The bacterial infections include cloctridium dificile, salmonella spp, shigella spp, *H. pylori*, eiserichia coli, campylobacter spp, *Yersinia enterocolitica,* mycobacterium tuberculosis, mycobacterium avium intracellurale complex. The parasitic infections include cryptosporidium, microsporidium, entamoeba histolytica, giardia lamblia, *Strongyloides stercoralis. The fungal infections include histoplasma capsulatum, candida albicans, candida tropicalis, mucormyces spp. The gastrointestinal infections have varying presentations but the commonest presentation is diarrhea.* 

*Mucosal injuries and ulceration of the gastrointestinal tract has been reported in patients with immunodeficiency. Many factors had been associated with ulcer formation and propagation in these patients. Some of these factors include stress, impairment of native cytoprotection of the gastrointestinal mucosa, drugs and infections especially helicobacter pylori. Complications that had resulted from gastrointestinal mucosa injury and ulceration include perforation, penetration, peritonitis and gastrointestinal bleeding.* 

*Diverticular disease had been reported in immunocompromised patients especially in post transplant patients on immunosuppressive therapy. The clinical presentation varies from asymptomatic to peritonitis. Complicated diverticulitis which was reported in 1.1% of renal transplant patients can presents as intestinal perforation, abscess, phlegmon or fistula.* 

180 Immunodeficiency

malignancy

*the commonest presentation is diarrhea.* 

*peritonitis and gastrointestinal bleeding.* 

estimated that the GIT contains about 60% of the total body lymphocyte. The immune cells

The gastrointestinal tract associated lymphoid tissue, can be divided into three sectors. The first is represented by the pharyngeal tonsils, the appendix, and the large aggregates of nodules known as Peyer patches located at intervals throughout the small intestine. The second sector includes the lymphocytes and plasma cells that populate the basement membrane (lamina propria) of the small intestine, the area of loose connective tissue above the supporting tissue of the mucosal lining extending into the villi. The third sector comprises lymphocytes that lie between the epithelial cells in the mucosa. The interaction between these cells of the lymphatic system and the threatening agent is the basis of defense in the gastrointestinal tract. The gastrointestinal tract also posses other protective measures which include tight epithelial junctions, the digestive enzymes, the acidic gastric fluid, the

However the gastrointestinal tract is particularly at risk of infectious and non infectious injuries because of the following reasons – because of their close proximity to the external environment and continuous exposure to myriad of food and other infectious and non infectious antigens, the mucosa is maintained in physiologic inflammatory state characterized by presence of proinflammatory cytokines, marked expression of CCR5 and

In immunocompromised patients the normal defenses are disrupted, leading to a wide range of clinical and pathogenic consequences. This usually leads to various disease conditions that can be classified into one of several general categories: infections, mucosal injury and ulceration, biliary tract diseases, diverticular disease, pancreatitis, and

The infections may be bacterial, viral, fungal, or parasitic and may infect one or more gut segments between the mouth and anus. The viral infections that had been reported in these patients include cytomegalovirus, herpes simplex, human papilloma virus, ebstein barr virus and rota virus. The bacterial infections include cloctridium dificile, salmonella spp, shigella spp, *H. pylori*, eiserichia coli, campylobacter spp, *Yersinia enterocolitica,* mycobacterium tuberculosis, mycobacterium avium intracellurale complex. The parasitic infections include cryptosporidium, microsporidium, entamoeba histolytica, giardia lamblia, *Strongyloides stercoralis. The fungal infections include histoplasma capsulatum, candida albicans, candida tropicalis, mucormyces spp. The gastrointestinal infections have varying presentations but* 

*Mucosal injuries and ulceration of the gastrointestinal tract has been reported in patients with immunodeficiency. Many factors had been associated with ulcer formation and propagation in these patients. Some of these factors include stress, impairment of native cytoprotection of the gastrointestinal mucosa, drugs and infections especially helicobacter pylori. Complications that had resulted from gastrointestinal mucosa injury and ulceration include perforation, penetration,* 

CXCR4 chemokine receptor that promotes HIV entry into the mucosa cells.

in the GIT are organized into distinct anatomic and functional sub compartments..

lysozyme and the high flow of the gastrointestinal fluid.

*Acute pancreatitis in immunocompromised patients are not common. It has been associated with alcohol ingestion, billiary stones, malignancy, hepatitis B and cytomegalovirus infection. Acute pancreatitis markedly increase the morbidity and mortality associated with immunodeficiency. The clinical presentation is usually atypical.* 

*There is increase in prevalence of both common and uncommon gastrointestinal malignancies in patients with immune deficiency. Decreased immune surveillance, continuous mucosa inflammation, gastrointestinal infections, ingestion of carcinogens including medications are some of the factors suspected to be responsible for the heightened prevalence of malignancy in these patients. Also cigarette smoking, sclerosing cholangitis, crohns syndrome and splenectomy had been reported as risk factor for the development of gastrointestinal malignancy in these patients. The gastrointestinal malignancies that have been associated with immunosuppression include Kaposi sarcoma, colorectal carcinoma, post transplant lymphoproliferative lymphoma, gastric mucosa associated lymphoma. The malignancies are initially asymptomatic however acute abdomen from perforation or obstruction and gastrointestinal bleeding are the usual though late presentations.* 

The commonly experienced gastrointestinal (digestive) complications; include oral lesions, esophageal lesions, diarrhea, and anorectal diseases (disease that affects the anus and/or rectum). The oral lesions are aphthous ulcer, oral thrush (candidiasis), oral wart, oral hairy leukoplakia, Kaposi sarcoma.

The oesophageal lesions include oesophageal candidiasis, oesopheal herpes simplex, cytomegalovirus, aphthous ulcer, malignancy, and reflux oesophagitis manifesting as dysphagia, odynophagia, and sensation of food sticking in the throat.

The anorectal lesions which are usually seen in immunocompromised patients with AIDS include herpes simplex infection, gonorhoea, syphilis, anal wart(condylomata) and Chlamydia.

Diarhoea is a common clinical presentation in immunocompromised patients independent of the cause. This has been attributed to gastrointestinal infections, malabsorption, medications etc.
