Homework # 2

1. Homework # 2 A2 Subsection Dr. Sandra Navarra USTFMS

2. 2. Classification of HIV and Expanded AIDS Surveillance Case Definition

3. Category A consists of one or more of the conditions listed below in an adolescent or adult (greater than or equal to 13 years) with documented HIV infection. Conditions listed in Categories B and C must not have occurred. • Asymptomatic HIV infection • Persistent generalized lymphadenopathy • Acute (primary) HIV infection with accompanying illness or history of acute HIV infection

4. Category B • Category B consists of symptomatic conditions in an HIV-infected adolescent or adult that are not included among conditions listed in clinical Category C. • Shouldmeet at least one of the following criteria • the conditions are attributed to HIV infection or are indicative of a defect in cell-mediated immunity • the conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection. • Conditions in clinical Category B include, but are not limited to: • Bacillary angiomatosis • Candidiasis, oropharyngeal (thrush) • Candidiasis, vulvovaginal; persistent, frequent, or poorly responsive to therapy • Cervical dysplasia (moderate or severe)/cervical carcinoma in situ • Constitutional symptoms, such as fever (38.5 C) or diarrhea lasting greater than 1 month • Hairy leukoplakia, oral • Herpes zoster (shingles), involving at least two distinct episodes or more than one dermatome • Idiopathic thrombocytopenic purpura • Listeriosis • Pelvic inflammatory disease, particularly if complicated by tubo-ovarian abscess • Peripheral neuropathy

5. Category C includes the clinical conditions listed in the AIDS surveillance case definition. • Once a Category C condition has occurred, the person will remain in Category C

6. Category C conditions • Candidiasis of bronchi, trachea, or lungs • Candidiasis, esophageal • Cervical cancer, invasive * • Coccidioidomycosis, disseminated or extrapulmonary • Cryptococcosis, extrapulmonary • Cryptosporidiosis, chronic intestinal (greater than 1 month's duration) • Cytomegalovirus disease (other than liver, spleen, or nodes) • Cytomegalovirus retinitis (with loss of vision) • Encephalopathy, HIV-related

7. Category C Conditions • Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis • Histoplasmosis, disseminated or extrapulmonary • Isosporiasis, chronic intestinal (greater than 1 month's duration) • Kaposi's sarcoma • Lymphoma, Burkitt's (or equivalent term) • Lymphoma, immunoblastic (or equivalent term) • Lymphoma, primary, of brain • Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary • Mycobacterium tuberculosis, any site (pulmonary * or extrapulmonary) • Mycobacterium, other species or unidentified species, disseminated or extrapulmonary • Pneumocystiscarinii pneumonia • Pneumonia, recurrent * • Progressive multifocal leukoencephalopathy • Salmonella septicemia, recurrent • Toxoplasmosis of brain • Wasting syndrome due to HIV

9. 3. List possible conditions to explain this patient’s cervical lymphadenopathy. • HIV infection • Kaposi's sarcoma • Tuberculosis • MulticentricCastleman’s disease • Lymphoma • Toxoplasmosis • Cryptococcus • Bacillary angiomatosis • Cytomegalovirus infection

10. 3. List possible conditions to explain this patient’s cervical lymphadenopathy. a. HIV infection • Disorders of the hematopoietic system including lymphadenopathy are common throughout the course of HIV infection and may be the direct result of HIV, manifestations of secondary infection or neoplasms. • Persistent generalized lymphadenopathy serve as its early clinical manifestation. • This condition is defined as the presence of enlarged lymph nodes (>1cm) in two or more extrainguinal sites for >3 months without an obvious cause • The lymphadenopathy is due to marked follicular hyperplasia in the node in response to HIV infection

11. 3. List possible conditions to explain this patient’s cervical lymphadenopathy. a. HIV infection • In HIV patients with CD4+ T cell counts > 200/uL, the differential diagnosis of lymphadenopathy includes Kaposi sarcoma, tuberculosis, castleman’s disease and lymphoma. • In HIV patients with more advanced disease, lymphadenopathy may also be due to toxoplasmosis, systemic fungal infection or bacillary angiomatosis.

12. 3. List possible conditions to explain this patient’s cervical lymphadenopathy. b. Kaposi sarcoma Immunocompromised patients with HHV-8 infection may present with fever, splenomegaly, lymphoid hyperplasia, pancytopenia or rapid onset KS. c. Tuberculosis Lymphadenopathy is the most common presentation of extrapulmonary TB which occurs more commonly in immuno-compromised patients especially those infected with HIV due to the impaired cell-mediated immunity essential for defense against TB.

13. 3. List possible conditions to explain this patient’s cervical lymphadenopathy. d. MulticentricCastleman’s disease - abnormal overgrowth of lymph nodes with high fevers, anemia, weight loss, loss of appetite, and low white blood cell counts due to the overproduction of interleukin 6. e. Lymphoma - higher incidence among HIV patients characterized by lymphadenopathy, fever of unknown origin, weight loss, pruritus, anorexia, fatigue

14. 3. List possible conditions to explain this patient’s cervical lymphadenopathy. f. Toxoplasmosis - a parasitic disease caused by Toxoplasmagondii presenting with swollen lymph nodes, or muscle aches and pains that last for a month or more. Immunocompromised patients, such as those with HIV/AIDS may develop severe toxoplasmosis which can cause damage to the brain (encephalitis) or the eyes (necrotizing retinochoroiditis). g. Cryptococcus infection - most commonly present with meningoencephalitis, headache, nausea, dementia, irritability caused by Cryptococcus neoformans

15. 3. List possible conditions to explain this patient’s cervical lymphadenopathy. h. Bacillary angiomatosis - characterized by the proliferation of blood vessels, resulting in tumour-like masses in the skin and other organs (lymph nodes, brain, bone marrow, spleen, liver) caused by Bartonellahenselae or Bartonellaquintana i. Cytomegalovirus infection - CMV is an important pathogen when CD4+ cell counts fall below 50-100/uL, producing lymphadenopathy, retinitis, colitis, and disseminated disease.

16. 4. Enumerate rheumatologic conditions in HIV-infected individuals

17. HIV-associated Rheumatic Diseases • disorders of the joints and muscles that can result from the HIV infection. • Painful joints and muscles are usually the first and most common complaints. • HIV-associated Rheumatic Diseases are: • Reactive arthritis – Reiter’s syndrome, Psoriatic Arthritis • HIV-associated arthropathy • Painful articular syndrome • Diffuse infiltrative lymphocytosis syndrome (DILS) • Fibromyalgia, septic arthritis, vasculitis Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

18. Reiter’s Syndrome • a triad of arthritis, urethritis & conjunctivitis • usually develops following an intestinal or a genital/urinary tract infection Psoriatic Arthritis • type of inflammatory arthritis that affects 10-30% of people suffering from the chronic skin condition psoriasis • exact cause unknown; genetic cause? Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

19. Reiter’s Syndrome & Psoriatic Arthritis • Occur with increasing frequency as the competency of the immune system declines • Related to an increase in infections with organisms that trigger a reactive arthritis with progressive immunodeficiency or to a loss of important regulatory T cells. Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

20. HIV-associated Arthropathy • Characterized by subacuteoligoarticular arthritis developing over a period of 1-6 weeks and lasting 6 weeks to 6 months • Generally involves the larger joints (knees and ankles) • Non-erosive with only a mild inflammatory response • NSAIDs are marginally helpful • Intra-articularglucocorticoids have been more useful in pain relief Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

21. Painful Articular Syndrome • 10% of AIDS patients • Presents as acute severe sharp pain in the affected joint (knees, elbows and shoulders) • Episodes last 2-24 hrs • Cause is unclear; however, it may be a result from a direct effect of HIV on the joint. • Condition is reminiscent of the fact that other lentiviruses (caprine arthritis-encephalitis virus) are capable of causing arthritis Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

22. Diffuse Infiltrative Lymphocytosis Syndrome (DILS) • Autoimmune disease that occurs with an increased frequency in HIV patients • Parotid gland enlargement, dry eyes, dry mouth associated with lymphocytic infiltrates of the salivary gland and lung • Infiltrates predominantly CD8+ T cells Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

23. Other Rheumatologic Disorders associated with HIV Patients • There have been reports of leukocytoclastic vasculitis in the setting of zidovudine therapy. • CNS angiitis and polymyositis have also been reported. • Septic arthritis = due to S. aureus, systemic fungal infections Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

24. 5. Describe the features/treatment of TB in the HIV patient, which may differ from that in a non-HIV patient

25. TB in an HIV Patient • A new TB infection acquired by an HIV infected patient may evolve to active disease in weeks rather than months or years. • When CMI is only partially compromised, pulmonary tuberculosis presents in a typical manner. • In late stages of HIV infection, a primary tuberculosis-like pattern, with diffuse interstitial or miliary infiltrates, little or no cavitation, and intrathoraciclymphadenopathy is more common. • Sputum smears may be positive less frequently.

26. TB in an HIV Patient • Extrapulmonary TB is more common (lymphatic, disseminated, pleural and pericardial are the most common) • Atypical radiographic findings, lack of classic granuloma formation in late stages, negative TST.

27. Treatment Regimen

28. Treatment • Standard treatment are equally efficacious, with more pronounced adverse effects. • Increased frequency of drug interactions between antiretroviral therapy and rifamycins • Development of of Rifampin monoresistance. • Substitute rifabutin to rifampin.

29. 6. Indications for initiation of anti-retroviral therapy in patients with HIV infection • Therapy should be initiated in patients with a CD4 count of <200 cells/microliter or in the symptomatic patient (with AIDS, thrush, or unexplained fever) regardless of the CD4 count or viral load. • In the asymptomatic patient, if the CD4 count is between 200 and 350 cells/microliter, initiation or ART is recommended, although some controversy still exists. Initiation of ART depends on the patient’s readiness, comorbidities, and drug toxicities.

30. 6. Indications for initiation of anti-retroviral therapy in patients with HIV infection • In the asymptomatic patient, if the HIV RNA is >100,000 copies/ml, initiation of the highly reactive ART is recommended although some controversy exists. Initiation of ART depends on the patient’s readiness, comorbidities, and drug toxicities.