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agent, which is also used for prevention of P. jiroveci pneumonia, is effective against T. gondii . Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the white matter of the brain caused by the JC virus, a DNA papovavirus that attacks the oligodendrocytes. 66 PML advances slowly, and is characterized by progressive limb weakness, sensory loss, difficulty controlling the digits, visual disturbances, subtle alterations in mental status, hemiparesis, ataxia, diplopia, and seizures. 66 The mortality rate is high, and the average survival time is 2 to 4 months after diagnosis. Diagnosis is suspected based on clinical findings and an MRI, and confirmed by the presence of the JC virus in the cere- brospinal fluid. 66 There is no proven cure for PML, but improvement can occur after starting effective HAART. Malignancies Persons with AIDS have a high incidence of certainmalig- nancies, especially Kaposi sarcoma (KS), non-Hodgkin lymphoma, and noninvasive cervical carcinoma. The increased incidence of malignancies probably is a func- tion of impaired cell-mediated immunity. As persons with HIV infection are living longer, there has been increasing incidence of age- and gender-specific malig- nancies. 67 Non–AIDS-defining malignancies account for more morbidity and mortality than AIDS-defining malignancies in the HAART era. Kaposi sarcoma is a malignancy of the endothelial cells that line small blood vessels. 68 An opportunis- tic cancer, KS occurs in immunosuppressed persons (e.g., transplant recipients or persons with AIDS). Kaposi sarcoma was one of the first and most com- mon opportunistic cancers associated with AIDS. Since the introduction of HAART, the incidence of KS has decreased dramatically but has not reached zero. There is evidence linking KS to a herpesvirus (herpesvirus 8 [HHV-8], also called KS-associated herpes virus [KSHV]). 68 The virus is readily transmit- ted through homosexual and heterosexual activities; however, there is a disproportionately higher inci- dence of KS in men who have sex with men com- pared with women and other men. Maternal–infant transmission also can rarely occur. The virus has been detected in saliva from infected persons, and other nonsexual modes of transmission are suspected. The lesions of KS can be found on the skin and on any mucosal surface in the oral cavity, gastrointestinal tract, and lungs. More than 50% of people with skin lesions also have gastrointestinal lesions. The disease usually begins as one or more macules, papules, or violet skin lesions that enlarge and become darker (Fig. 16-11). Tumor nodules frequently are located on the trunk, neck, and head, especially the tip of the nose. They usually are painless in the early stages, but discomfort may occur as the tumor develops. Invasion of internal organs, including the lungs, gastrointes- tinal tract, and lymphatic system, commonly occurs. Gastrointestinal tract KS is often asymptomatic, but can cause pain, bleeding, or obstruction. 68

HIV infection. 63 Aphthous ulcers presumed secondary to HIV are also common. Persons experiencing these infections usually complain of painful swallowing or retrosternal pain. Endoscopy or barium esophagogra- phy is required for definitive diagnosis. Diarrhea or gastroenteritis is a common complaint in persons with HIV infection. Although diarrhea is often a side effect of medications used to treat HIV, it should be evaluated for the same common causes as in the general population. The most common pro- tozoal opportunistic infection that causes diarrhea is Cryptosporidium parvum. Clinical features of cryp- tosporidiosis can range from mild diarrhea to severe, watery diarrhea with a loss of up to several liters of water per day, as well as malabsorption, electrolyte disturbances, dehydration, and weight loss. Other organisms that cause gastroenteritis and diarrhea are Salmonella, CMV, Clostridium difficile, Escherichia coli, Shigella, Giardia, and microsporidia. 63 These organisms are identified by examination of stool cul- tures or endoscopy. Nervous SystemManifestations. Human immunode- ficiency virus infection, particularly in the late stages of severe immunocompromise, leaves the nervous system vulnerable to an array of neurologic disorders, including neurocognitive disorders, toxoplasmosis, and progres- sive multifocal leukoencephalopathy. HIV-associated neurocognitive disorders (HANDs) is a syndrome of cognitive impairment with motor dys- function or behavioral/psychosocial symptoms associ- ated with HIV infection itself. 64 In 2007, the National Institute of Mental Health and National Institute of Neurologic Diseases and Stroke developed a new clas- sification with standardized diagnostic criteria for HANDs. The three conditions comprising HANDs are HIV-associated asymptomatic neurocognitive impairment, HIV-associated mild neurocognitive dis- order, and HIV-associated dementia, formerly known as AIDS dementia complex . 64 The clinical features of HIV-associated dementia, which is usually a late complication of HIV infection, include impairment of attention and concentration, slowing of mental and motor speed and agility, and apathetic behavior. There is no specific treatment for HAND, but HAART com- prised of medications which penetrate the blood-brain barrier is considered the best therapeutic option at this time. Toxoplasmosis is a common opportunistic infection in persons with AIDS. The organism responsible, T. gondii, is a parasite that most often affects the CNS. 65 Toxoplasmosis usually is a reactivation of a latent T. gondii infection that has been dormant in the CNS. The typical presentation includes fever, headaches, and neu- rologic dysfunction, including confusion and lethargy, visual disturbances, and seizures. Computed tomogra- phy scans or, preferably, magnetic resonance imaging (MRI) should be performed immediately to detect the presence of neurologic lesions. Prophylactic treatment with trimethoprim-sulfamethoxazole or an alternative