Homework # 2 A2 Subsection Dr. Sandra Navarra USTFMS

2. Classification of HIV and Expanded AIDS Surveillance Case Definition

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

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

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

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

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 Pneumocystis carinii pneumonia Pneumonia, recurrent * Progressive multifocal leukoencephalopathy Salmonella septicemia, recurrent Toxoplasmosis of brain Wasting syndrome due to HIV

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

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

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.

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.

3. List possible conditions to explain this patient’s cervical lymphadenopathy. d. Multicentric Castleman’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

3. List possible conditions to explain this patient’s cervical lymphadenopathy. f. Toxoplasmosis - a parasitic disease caused by Toxoplasma gondii 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

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 Bartonella henselae or Bartonella quintana i. Cytomegalovirus infection - CMV is an important pathogen when CD4+ cell counts fall below /uL, producing lymphadenopathy, retinitis, colitis, and disseminated disease.

4. Enumerate rheumatologic conditions in HIV-infected individuals

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 Harrison’s Principles of Internal Medicine, 17 th Edition. McGraw-Hill. USA

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 Harrison’s Principles of Internal Medicine, 17 th Edition. McGraw-Hill. USA

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 Harrison’s Principles of Internal Medicine, 17 th Edition. McGraw-Hill. USA

HIV-associated Arthropathy Characterized by subacute oligoarticular 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-articular glucocorticoids have been more useful in pain relief Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo Harrison’s Principles of Internal Medicine, 17 th Edition. McGraw-Hill. USA

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 Harrison’s Principles of Internal Medicine, 17 th Edition. McGraw-Hill. USA

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 Harrison’s Principles of Internal Medicine, 17 th Edition. McGraw-Hill. USA

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 Harrison’s Principles of Internal Medicine, 17 th Edition. McGraw-Hill. USA

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

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 intrathoracic lymphadenopathy is more common. Sputum smears may be positive less frequently.

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.

Treatment Regimen

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.

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.

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.