**3. Hepato billiary system in immunocompromised**

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

The bile plays an important role in breaking down of fats, the source of cellular energy. It is necessary for the absorption of many vitamins and other fat related substances. It also participates in the excretion of many product of metabolism including bilirubin, bile acid and medications.

Pattern of Clinical Presentations in Immunocompromised Patient 183

lung diseases in immunocompromised patients however noninfectious diseases are not

Pulmonary infections decisively contribute to morbidity and mortality in immunocompromised patients. The prevalence of both the common infections implicated in community acquired pneumonia and some uncommon infections including opportunistic infections are increased in immunocompromised patients. Among the infections encountered are streptococcus pneumoniae, klebsiella pneumonia, haemophilus influenza, pseudomonas aeruginosa, actinobacter spp, fusobacterium nucleatum, bacteroids melaninogenicus, bacteroids fragilis, mycobacterium tuberculi, mycobacterium avium intracellurale, pneumocystis carinii (jirovecii), norcadia spp, coccidomyces spp, aspergilus spp, *Rhodococcus equi* etc. The infections usually present as pneumonia, suppurative lung

The spectrum of noninfectious lung injury and response in the immunosuppressed host includes interstitial edema, interstitial fibrosis, diffuse idiopathic pneumonia, acute respiratory distress syndrome, obliterative bronchiolitis, alveolar hemorrhage, pulmonary embolism, radiation pneumonitis, drug toxicity, progression or recurrence of neoplastic disorders, chemotherapy, transfusion and transplant related lung injuries. The clinical manifestations of various non infectious complications in immunocompromised patients are

Clinical approach to respiratory tract diseases in immunocompromised patients are classified into five categories. The first situation is defined by a slow progression of the disease, the absence of fever (or mild fever), and diffuse opacities. Pulmonary oedema, pulmonary localisation of the underlying disease, or toxic treatment induced pneumonitis are usually the cause. Non-specific pneumonitis may also be responsible, particularly in

The second situation, defined by a rapid progression of the condition, fever, and diffuse opacities, usually indicates an opportunistic pneumonia but, in a few cases, a hypersensitivity drug induced pneumonitis (for example, to methotrexate) or a localisation of the underlying disease—for example, in cases of vasculitis or collagen vascular disease may be the cause. In the absence of new extrapulmonary symptoms, *Pneumocystis carinii* must be considered. In contrast, the presence of new extrapulmonary symptoms or signs suggests an association or another opportunistic infection such as cytomegalovirosis,

In the third situation the clinical feature is that of bacterial pneumonia or sepsis with ARDS. The pathogens responsible are usually*Streptococcus pneumoniae* or *Haemophilus influenzae*

The fourth situation with rapid to moderate progression of the condition, fever, nodules or round infiltrates evolving towards dissemination and/or cavitation is highly suggestive of fungal pneumonia. However, legionellosis, tuberculosis and even pulmonary infarction or

specific localisation of vasculitis may also result in similar manifestations.

disease, interstitial lung disease and obstructive lung diseases

non specific and may mimic infections.

bone marrow transplant recipients.

cryptococcosis, toxoplasmosis, or tuberculosis.

and, to a lesser degree, *Legionella* spp.

uncommon.

The hepatobilliary system receives dual blood supply, from the portal and systemic circulation. Hence in immunocompromised patient the hepatobilliary system is exposed to many infectious and non infectious antigens. This predisposes the patient to many disease conditions relating/affecting the system.

Immunodeficiency states resulting from AIDS, cytotoxic chemotherapy, radiation, organ transplantation and common variable immunodeficiency disorders have been associated with hepatobilliary disease. These disorders that have been reported in immunocompromised patients include infectious hepatitis, granulomatous hepatitis, alcoholic liver disease, cholangiopathy, hepatocellular carcinoma, schistosomiasis, haemangioma and hepatic adenoma. Nodular regenerative hyperplasia of the liver has also been reported in patients with combined variable immunodeficiency syndrome.

There are various clinical manifestations relating to this system in these patients. In a study of patients with common variable immunodeficiency syndrome with nodular regenerative hyperplasia 39% of the patients were asymptomatic but had deranged liver functions, 46% had jaundice, 46% had hepatomegaly, 23% had pruritus, 15% had ascitis, 15% had oesophageal varices. Also jaundice and hepatomegaly is a common presentation in immunocompromised patients resulting from opportunistic and conventional infections of either hepatobilliary or other systems. Other manifestations include portal hypertension, cirrhosis, primary and secondary malignancies of the liver and billiary tree, and hepatic failure.

#### **4. Respiratory system in immunocompromised**

The immune system in the airways consists of both innate and specific immunity. Innate immunity consists of mechanical defenses, antimicrobial molecules generated in the airways, and phagocytic defenses provided by the resident alveolar macrophages and the polymorphonuclear leukocytes (PMNs) that are recruited into the lung in response to infection. The specific immunity are usually initiated by the dendritic cell that act as the antigen presenting cell. They migrate to the regional lymphoid tissue to initiate the primary response with generation of memory B and T cells.

This sophisticated immune defense system effectively protects the host from infections and other immunodeficiency related diseases of the respiratory tract. However this function is impaired in immunocompromised individuals thus exposing them to many diseases of the airways.

Patients with compromised immune function suffer from a wide variety of infectious and non infectious lung insults. Infections are the most common cause of both acute and chronic lung diseases in immunocompromised patients however noninfectious diseases are not uncommon.

182 Immunodeficiency

failure.

airways.

and medications.

conditions relating/affecting the system.

The bile plays an important role in breaking down of fats, the source of cellular energy. It is necessary for the absorption of many vitamins and other fat related substances. It also participates in the excretion of many product of metabolism including bilirubin, bile acid

The hepatobilliary system receives dual blood supply, from the portal and systemic circulation. Hence in immunocompromised patient the hepatobilliary system is exposed to many infectious and non infectious antigens. This predisposes the patient to many disease

Immunodeficiency states resulting from AIDS, cytotoxic chemotherapy, radiation, organ transplantation and common variable immunodeficiency disorders have been associated with hepatobilliary disease. These disorders that have been reported in immunocompromised patients include infectious hepatitis, granulomatous hepatitis, alcoholic liver disease, cholangiopathy, hepatocellular carcinoma, schistosomiasis, haemangioma and hepatic adenoma. Nodular regenerative hyperplasia of the liver has also

There are various clinical manifestations relating to this system in these patients. In a study of patients with common variable immunodeficiency syndrome with nodular regenerative hyperplasia 39% of the patients were asymptomatic but had deranged liver functions, 46% had jaundice, 46% had hepatomegaly, 23% had pruritus, 15% had ascitis, 15% had oesophageal varices. Also jaundice and hepatomegaly is a common presentation in immunocompromised patients resulting from opportunistic and conventional infections of either hepatobilliary or other systems. Other manifestations include portal hypertension, cirrhosis, primary and secondary malignancies of the liver and billiary tree, and hepatic

The immune system in the airways consists of both innate and specific immunity. Innate immunity consists of mechanical defenses, antimicrobial molecules generated in the airways, and phagocytic defenses provided by the resident alveolar macrophages and the polymorphonuclear leukocytes (PMNs) that are recruited into the lung in response to infection. The specific immunity are usually initiated by the dendritic cell that act as the antigen presenting cell. They migrate to the regional lymphoid tissue to initiate the primary

This sophisticated immune defense system effectively protects the host from infections and other immunodeficiency related diseases of the respiratory tract. However this function is impaired in immunocompromised individuals thus exposing them to many diseases of the

Patients with compromised immune function suffer from a wide variety of infectious and non infectious lung insults. Infections are the most common cause of both acute and chronic

been reported in patients with combined variable immunodeficiency syndrome.

**4. Respiratory system in immunocompromised** 

response with generation of memory B and T cells.

Pulmonary infections decisively contribute to morbidity and mortality in immunocompromised patients. The prevalence of both the common infections implicated in community acquired pneumonia and some uncommon infections including opportunistic infections are increased in immunocompromised patients. Among the infections encountered are streptococcus pneumoniae, klebsiella pneumonia, haemophilus influenza, pseudomonas aeruginosa, actinobacter spp, fusobacterium nucleatum, bacteroids melaninogenicus, bacteroids fragilis, mycobacterium tuberculi, mycobacterium avium intracellurale, pneumocystis carinii (jirovecii), norcadia spp, coccidomyces spp, aspergilus spp, *Rhodococcus equi* etc. The infections usually present as pneumonia, suppurative lung disease, interstitial lung disease and obstructive lung diseases

The spectrum of noninfectious lung injury and response in the immunosuppressed host includes interstitial edema, interstitial fibrosis, diffuse idiopathic pneumonia, acute respiratory distress syndrome, obliterative bronchiolitis, alveolar hemorrhage, pulmonary embolism, radiation pneumonitis, drug toxicity, progression or recurrence of neoplastic disorders, chemotherapy, transfusion and transplant related lung injuries. The clinical manifestations of various non infectious complications in immunocompromised patients are non specific and may mimic infections.

Clinical approach to respiratory tract diseases in immunocompromised patients are classified into five categories. The first situation is defined by a slow progression of the disease, the absence of fever (or mild fever), and diffuse opacities. Pulmonary oedema, pulmonary localisation of the underlying disease, or toxic treatment induced pneumonitis are usually the cause. Non-specific pneumonitis may also be responsible, particularly in bone marrow transplant recipients.

The second situation, defined by a rapid progression of the condition, fever, and diffuse opacities, usually indicates an opportunistic pneumonia but, in a few cases, a hypersensitivity drug induced pneumonitis (for example, to methotrexate) or a localisation of the underlying disease—for example, in cases of vasculitis or collagen vascular disease may be the cause. In the absence of new extrapulmonary symptoms, *Pneumocystis carinii* must be considered. In contrast, the presence of new extrapulmonary symptoms or signs suggests an association or another opportunistic infection such as cytomegalovirosis, cryptococcosis, toxoplasmosis, or tuberculosis.

In the third situation the clinical feature is that of bacterial pneumonia or sepsis with ARDS. The pathogens responsible are usually*Streptococcus pneumoniae* or *Haemophilus influenzae* and, to a lesser degree, *Legionella* spp.

The fourth situation with rapid to moderate progression of the condition, fever, nodules or round infiltrates evolving towards dissemination and/or cavitation is highly suggestive of fungal pneumonia. However, legionellosis, tuberculosis and even pulmonary infarction or specific localisation of vasculitis may also result in similar manifestations.

The last situation is certainly the most complex. The clinician is confronted with focal pulmonary infiltrates which do not respond to antibiotics. Opportunistic agents such as *Mycobacteria* spp, *Nocardia* spp, or *Rhodococcus equi*, organising pneumonia or tumour may be the cause.

Pattern of Clinical Presentations in Immunocompromised Patient 185

There are many organisms that are associated with infection of or manifestations in the skin in patients with immunodeficiency. The infections could be as a result of conventional or opportunistic infection. These infections include viral, bacterial, fungal and parasitic. The organisms that have been associated with dermatological infections or manifestation in immunocompromised patients are herpes simplex virus, varicella zoster virus, cytomegalovirus and pappiloma virus, staphylococcus spp, streptococcus spp, pseudomonas spp, atypical mycobacterium spp, the fungal infections including malasezia furfur, candidiasis, norcadia spp, Cryptococcus neoformans, Aspergillus species,

The commonly reported dermatological lesions in immunocompromised patients include dermatitis, seborrheic dermatitis, folliculitis, dermatophytes including pityriasis versicolor, wart, Kaposi sarcoma, herpes zoster, acne vulgaris, urticaria, pruritus, psoriasis, malasma and erythema multiforme. Other Skin lesions including pustules, gangrenous cellulitis, erythematous subcutaneous nodules, hemorrhagic bullae, petechiae, ecchymoses, and

Cutaneous manifestations often are accompanied by fever, defined as an isolated temperature of 38.3°C (101°F), that cannot be attributed to exogenous causes, such as blood

Immune responses in the CNS are common, despite its perception as a site of immune privilege. These responses can be mediated by resident microglia and astrocytes, which are innate immune cells without direct counterparts in the periphery. Furthermore, CNS immune reactions often take place in virtual isolation from the innate/adaptive immune interplay that characterizes peripheral immunity. However, microglia and astrocytes also engage in significant cross-talk with CNS-infiltrating T cells and other components of the

Microglia are key players of the immune response in the central nervous system (CNS) and being the resident innate immune cells, they are responsible for the early control of infections and for the recruitment of cells of the adaptive immune system required for pathogen clearance. The innate and adaptive immune responses triggered by microglia include the release of proinflammatory mediators. Although an efficient immune response is required for the defense against invading pathogens, an inflammatory response in the CNS may also lead to tissue injury and neurodegeneration. Engagement of Toll-like receptors (TLRs), a major family of pattern recognition receptors that mediate innate immunity but also link with the adaptive immune response, provides an important mechanism by which microglia are able to sense both pathogen and host derived ligands

Patients with immunodeficiency are at risk of a wide range of neurologic diseases including

ecthyma gangrenosum had also been reported in immunocompromised patients.

products, or a temperature above 38°C (100.4°F) that persists for more than 1 hour.

Paecilomyces, Rhizopus species, Candida tropicalis, and scabies.

**6. Central nervous system in immunocompromised** 

infections, neoplasms, and drug-related complications of therapy

innate immune system.

within the CNS.
