**5. Skin in immunocompromised**

Skin, once thought to be an inert structure, plays a vital role in protecting the individual from the external environment. The epidermis impedes penetration of microbial organisms, chemical irritation, and toxins, absorbs and blocks solar and ionized radiation, and inhibits water loss.

The stratum corneum, the outermost layer of the epidermis that results from the terminal differentiation of the keratinocytes, forms the primary layer of protection from the external environment. This layer of anucleated keratinocytes is composed of highly cross-linked proteinaceous cellular envelopes with extracellular lipid lamellae consisting of ceramides, free fatty acids, and cholesterol. The free fatty acids create an acidic environment that inhibits colonization by certain bacteria such as Staphylococcus aureus, providing further protection.

Apart from the physical barriers the skin also contain other innate immunomodulating substances and cells. This include cathelicidins, cytokines. neuropeptides, eicosanoids, reactive oxygen species and langhern cell which has phagocytic properties, and act as antigen presenting cell. The skin is consistently exposed to host of injuries because of their size and exposure to the environment. These coordinated protective barriers, cells and substances maintain the integrity of the skin.

In immunodeficiency state there is alteration in this innate immune state in the skin. This thus predisposes the skin to many injuries – infectious and non infectious. Dermatological manifestations are important healthcare concerns in patients with immunodeficiency state. About 25% of patients with immunodeficiency had been reported with dermatological injuries.

Subsequent invasion of the skin by various bacterial, viral, fungal, and parasitic agents spur infectious skin lesions, whereas non-infectious skin conditions mainly emerge from adverse drug reactions or certain inflammatory or malignant aetiologies. Thus microbial infections, inflammatory conditions, and neoplasms are the three main causes for the development of dermatological findings in immunocompromised patients.

There have been several reports detailing the high frequency of dermatological manifestations in HIV infected patients, 96% in India, 70% in Taiwan, 65.3% in France, 65.3% in Tanzania, 34% in Thailand, 32.6% in Iran. The dermatological manifestations in these patients may be as a result of primary dermatological infection, metastastic infection with primary in another organ or systemic infection.

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, Paecilomyces, Rhizopus species, Candida tropicalis, and scabies.

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 ecthyma gangrenosum had also been reported in immunocompromised patients.

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

### **6. Central nervous system in immunocompromised**

184 Immunodeficiency

be the cause.

water loss.

protection.

injuries.

**5. Skin in immunocompromised** 

substances maintain the integrity of the skin.

dermatological findings in immunocompromised patients.

primary in another organ or systemic infection.

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

Skin, once thought to be an inert structure, plays a vital role in protecting the individual from the external environment. The epidermis impedes penetration of microbial organisms, chemical irritation, and toxins, absorbs and blocks solar and ionized radiation, and inhibits

The stratum corneum, the outermost layer of the epidermis that results from the terminal differentiation of the keratinocytes, forms the primary layer of protection from the external environment. This layer of anucleated keratinocytes is composed of highly cross-linked proteinaceous cellular envelopes with extracellular lipid lamellae consisting of ceramides, free fatty acids, and cholesterol. The free fatty acids create an acidic environment that inhibits colonization by certain bacteria such as Staphylococcus aureus, providing further

Apart from the physical barriers the skin also contain other innate immunomodulating substances and cells. This include cathelicidins, cytokines. neuropeptides, eicosanoids, reactive oxygen species and langhern cell which has phagocytic properties, and act as antigen presenting cell. The skin is consistently exposed to host of injuries because of their size and exposure to the environment. These coordinated protective barriers, cells and

In immunodeficiency state there is alteration in this innate immune state in the skin. This thus predisposes the skin to many injuries – infectious and non infectious. Dermatological manifestations are important healthcare concerns in patients with immunodeficiency state. About 25% of patients with immunodeficiency had been reported with dermatological

Subsequent invasion of the skin by various bacterial, viral, fungal, and parasitic agents spur infectious skin lesions, whereas non-infectious skin conditions mainly emerge from adverse drug reactions or certain inflammatory or malignant aetiologies. Thus microbial infections, inflammatory conditions, and neoplasms are the three main causes for the development of

There have been several reports detailing the high frequency of dermatological manifestations in HIV infected patients, 96% in India, 70% in Taiwan, 65.3% in France, 65.3% in Tanzania, 34% in Thailand, 32.6% in Iran. The dermatological manifestations in these patients may be as a result of primary dermatological infection, metastastic infection with 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 innate immune system.

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 within the CNS.

Patients with immunodeficiency are at risk of a wide range of neurologic diseases including infections, neoplasms, and drug-related complications of therapy

CNS infections caused by infective agents are rare in immunocompetent host, but more frequent in immunocompromised patients. The spectrum of causative organisms may vary greatly, depending on the underlying malignancy, its treatment and various other factors. Infections that had been reported to cause neurological diseases in immunocompromised patients are as detailed below;

Pattern of Clinical Presentations in Immunocompromised Patient 187

cells. The bone marrow also harbours matured and maturing immune cells. However the physiological activities of both innate and acquired immunity in the musculoskeletal system

There is increased prevalence of musculoskeletal diseases especially infections in immunocompromised patients. Musculoskeletal syndromes that occur in HIV-infected patients include manifestations of drug toxicity, reactive arthritis, Reiter's syndrome, infectious arthritis, and myositis. Post transplant patients have developed myopathies and various bony and joint disorders. Myopathy and myositis have been reported in patients

Some other musculoskeletal disorders in patients with immunodeficiency include some syndromes with arthritis or myositis as one of the components eg Reiters syndrome,

The hallmark of the presentation is pain in the muscle, swelling of muscle, occasionally associated with fever and muscle atrophy. Arthralgia, swelling of the joint and when intervention is delayed distortion of the joint. Patient may develop cellulitis with or without abscess formation and osteomyelitis. There is need for prompt diagnosis and intervention as

The urogenital tract contain both cellular and non cellular innate immune components. This ensure the sterility of the urinary tract and part of the genital tract. In immunodeficiency state the urogenital tract are exposed to higher prevalence of both common and rare infections. The urogenital diseases that have been reported in immunocompromised patients include urinary tract infection, epididymitis, prostatitis, extensive condylomata of

The occurrence of urinary tract infection and its clinical impact is determined, as with any infectious disease, by the interaction between the virulence of the infecting organism and the host defense mechanisms that can be mobilized. In the case of urinary tract infections, an anatomically and functionally intact kidney and urinary tract are the primary host defenses, with phagocytic function and immune mechanisms coming into play to limit the

Defects in the immune system determine the clinical manifestations and severity of urinary tract infections (UTI) and the rates of complication. However they only have an indirect role in influencing susceptibility to infection. Of all the categories of immunocompromised hosts, the renal transplant patient is the one most susceptible to the direct and indirect consequences of urinary tract infections. The rates of UTI in diabetics, renal transplant, recipients, neutropenic patients, and patients with AIDS are primarily determined by the degree and duration of urinary tract manipulation, and the higher perineal prevalence of

potential pathogens that result from frequent hospitalization and antimicrobial use.

with diabetes mellitus and some primary immune deficiency disorders.

Dermatomyositis, Sjogrens syndrome, Polyomyositis and Psoriasis.

delay may lead to rapid spread of the infection in these patients.

**8. Urogenital system in immunocompromised** 

the urethra, renal abscess and other renal related diseases.

consequences of those infections.

are poorly documented.

Viral – herpes simplex virus, JC virus, cytomegalovirus, varicella zoster virus. Bacterial – staphylococcus spp, pneumococcus, haemophilus spp, mycobacterium tuberculosis, mycobacterium Avium/ Intracellulare Complex, Listeria spp, norcadia spp. fungal *– Cryptococcus neoformans, Aspergillus fumigatus, Zygomycetes (Mucor and Rhizopus), Candida albicans*, Coccidioides spp

Parasitic - toxoplasmosis, strongyloides.

Development of neurologic manifestations depends on a variety of factors, including therapy with drugs like antiretroviral drugs and the patient's overall degree of immunosuppression. Heavily immunocompromised patients like those after allogeneic stem cell transplantation (SCT) or previous T cell depleting treatment regimens (e.g. with fludarabine or alemtuzumab) are at highest risk for cerebral infections. . The infections can cause global or focal cerebral dysfunction, subhemispheric impairment, spinal cord injury and occasionally, peripheral nerve injury.

Thus, in the immunosuppressed patient with neurological involvement there are three interrelated areas to consider. First, has whatever caused the immunosuppression either directly or indirectly affected the nervous system? Second, are such problems due to an infection of the nervous system? And last, are there any medical complications that might produce a neurological disturbance? In assessing immunosuppressed patients, the clinician must remember that more than one of these factors may be involved in the neurological presentation.

Clinical presentations in these patients may include headache, signs and symptoms of increased intracranial pressure, and lateralizing signs appropriate to the area(s) of involvement. These symptoms can include behavioral, cognitive, and personality changes. Focal symptoms include hemiparesis, aphasia, and visual field defects. Ataxia, seizures, and cranial nerve palsies can also occur but are not as common.

Meningoencephalitis is a common presentation however the classical symptoms and signs may be absent in these patients.. Also cerebral toxoplasmosis, cerebral lymphoma and cerebral vascular accident in immunocompromised patients may have similarities in their clinical presentations. The nature of neurological manifestation in patients with impaired immune state also varies with the cause and the degree of the immunosuppression. There is need for high index of suspicion to avoid delay or misdiagnosis that may lead to delay in intervention.

#### **7. Musculoskeletal system in immunocompromised**

The immune cells and mediators had been implicated in some musculoskeletal diseases. The bone marrow is the source of various haematological cells including the primordial immune cells. The bone marrow also harbours matured and maturing immune cells. However the physiological activities of both innate and acquired immunity in the musculoskeletal system are poorly documented.

There is increased prevalence of musculoskeletal diseases especially infections in immunocompromised patients. Musculoskeletal syndromes that occur in HIV-infected patients include manifestations of drug toxicity, reactive arthritis, Reiter's syndrome, infectious arthritis, and myositis. Post transplant patients have developed myopathies and various bony and joint disorders. Myopathy and myositis have been reported in patients with diabetes mellitus and some primary immune deficiency disorders.

Some other musculoskeletal disorders in patients with immunodeficiency include some syndromes with arthritis or myositis as one of the components eg Reiters syndrome, Dermatomyositis, Sjogrens syndrome, Polyomyositis and Psoriasis.

The hallmark of the presentation is pain in the muscle, swelling of muscle, occasionally associated with fever and muscle atrophy. Arthralgia, swelling of the joint and when intervention is delayed distortion of the joint. Patient may develop cellulitis with or without abscess formation and osteomyelitis. There is need for prompt diagnosis and intervention as delay may lead to rapid spread of the infection in these patients.
