A 28-year-old man presents with weakness and an inability to speak "normally". He complains of fever, dry cough, and dyspnea. He has been treated for urethritis and genital warts in the past, and admits to bisexual behavior. He denies any IV drug use. A recent male partner developed pneumonia and lost over 10 lbs. He keeps a pet parrot. He reports a poor appetite, intermittent episodes of a non-productive cough and difficulty with breathing. Vital Signs: Pulse 85, BP 110/65. Temp 39C. Multiple violaceous patches, plaques, and nodules are noted on his back and legs. Auscultation of the lungs reveals scattered rales. He was disoriented to time and place. CBC: HCT 38, MCV 79, WBC 4,400 with predominance of neutrophils CD4+ T-lymphocyte count 95 per mm. Chest film shows bilateral interstitial and alveolar infiltrates. pO2 on room air= 54 mm Hg. What is causing his condition?
INFECTION: HIV gp120 binds CD4+ T-cells and destroys them. This results in deficient cell-mediated immunity, B-cell function, increased opportunistic and typical infections. CNS: You see Hodgkins and Non-Hodgkisn lymphoma (especially in the CNS). Toxoplasmosis and cryptococcus can infiltrate the CNS. Infected microglia are activated, release cytokines and have negative effects on the CNS. SYSTEMIC: CD4+ macrophages are infected by HIV, harbor it as a reservoir and allow it to disseminate systemically.
A 12 year old boy developed fever, malaise, myalgia, inability to eat, and irritability. Temp 102°F. Bilateral cervical adenopathy, ulcerative lesions on the hard and soft palate, gingiva, tongue, lip, and facial area. What would you expect to see on histologic analysis of these lesions?
HSV intranuclear inclusions. Note that the cells are not enlarged as they would be with CMV.
A 39-year-old navy nurse complained of fatigue, weight loss, night sweats and a productive cough. Generally in good health. Father died of heart attack, age 75; mother 80 y/o in good health. She served several tours on the USNS Comfort. She complained of heavy menses for many years.Thin, tired and pale appearing female; frequent coughing, HR 85, RR 20. A PPD test showed induration of 12 mm. A chest X-ray showed disseminated fibro-nodular densities. What would you likely see on biopsy of these densities?
Presence of apical cavitary lesions indicates that this is a secondary Tb infection. You would see giant cells, lymphocytes and caseating necrotizing granulomas.
A 62 year old female was discharged following an aortic valve replacement. She returns several days later with complaints of fever and malaise. On admission, a new systolic murmur is heard, and oral exam discloses whitish exudates in the mouth. The patient expires unexpectedly. C. albicans grows out of the blood cultures. What is causing her condition?
In healthy people, endocarditis will be very acute (for example s. aureus) because you need a very virulent organism to overcome host defenses. Candida is not one of these organisms and can more easily take root in a replaced valve like this patient has.
A 23 year old sexually active male complains of onset of a whitish and mucoid urethral discharge, dysuria, and urethral itching. Meatal erythema and tenderness and a demonstrable urethral discharge. Negative for Neisseria gonorrhea by gram stain and culture. What other conditions is she at risk for?
She likely has chlamydia. This puts her at risk for PID, reactive arthritis, keratitis (trachoma) and lymphogranuloma venereum.
Why do lymphomas have a propensity to arise in patients with HIV? What other carcinomas can arise due to this?
EBV latency and reactivation in immunocompromised patients because of CD8 dysfunction due to CD4 T-cell loss. Burkitt’s, Non-Hodgkins and certain subsets of Hodgkin lymphomas can be caused by EBV. Note that you also get hairy leukoplakia of the tongue due to squamous epithelial proliferation. Nasopharyngeal carcinoma can also be caused by EBV.
What is the pathogenesis of the condition shown below?
HIV infection -> CD4 depletion -> KSHV infection of spindle cells -> cytokine and growth factor release -> Endothelial proliferation and angiogenesis -> Kaposi sarcoma
Top cause of mortality in AIDS patients?
What is causing pneumonia in this AIDS patient?
Note the pink bubbly amorphous material in the alveoli indicative of PJP
What is causing pneumonia in this AIDS patient?
Note the intranuclear and intracytoplasmic inclusions indicative of CMV.
Histology of Tb in a patient with HIV?
They will have way more acid-fast bacilli (red snappers seen in MAC shown below) and fewer granulomas due to deficient Th1 response.
How can HSV cause blindness?
Direct infection of corneal epithelial cells that causes direct keratitis or immune reaction against the HSV that causes stromal opacification
Which of these is primary Tb and which is secondary Tb?
Right = granulomatous peripheral involvement with pleuritis indicates primary Tb. Left = cavitary, destructive, necrotic lesions seen in secondary Tb.
What are the clinical implications of a cavitary Tb infection?
Cavitation = open place of transmission of Tb with cough and systemic hematogenous spread.
What causes this?
Secondary Tb from the lung spreads hematogenously then seeds the lung and causes miliary Tb.
Is this a primary or secondary Tb lesion?
Note the white spot in the middle periphery of the lung. This is a ghon complex of primary Tb.
What other stain would you want to do on a patient who has a cavitary pulmonary lesion after acid-fast stain?
Silver stain for fungi
What causes the induration in a +PPD test? When might you see false PPDs? How do you account for this?
T-cell memory response. BCG vaccine will give a false positive. Immunosuppression will give a false negative test and should be confirmed with candida injection. If candida is negative, you know they are immunosuppressed.
Sequelae of Tb infection?
Osteomyelitis (Pott’s disease of vertebrae) and cranial nerve palsy (3rd w/ptosis)
Immune response critical for control of candida infection?
Th17 activation of neutrophils. Note that in general immunosuppression there may be neutropenia and have problems controlling candida infection.
What predisposes someone to Reiter’s syndrome (conjunctivitis + reactive arthritis)?
Enterics (shigella, salmonella, campylobacter, yersinia), STIs (chlamydia, gonorrhea) + HLA-B27
What cells are typical targets of the HIV virus?
CD4+ cells. This includes T-cells and cells of the monocytic-macrophage lineage.
Why are HIV patients at increased risk for epithelial malignancies?
Impaired immune surveillance mechanisms
Most common way HIV is transmitted?
How does HIV enter host cells?
HIV gp120 binds CD4 receptor -> gp120 binds CCR5 or CXCR4 coreceptor -> gp41 unfolds and penetrates plasma membrane -> Viral membrane fuses with host cell membrane
HIV target tissues
CNS and lymph nodes
Common causes of death in HIV patients
Reactivation of latent HSV or disseminated infection (bacterial and fungal). Note that respiratory tract infections are the chief causes of morbidity and mortality in patients with AIDS.
Suspected pathogen if a patient with AIDS presents with bilateral pulmonary congestion on radiographs
Most common malignancy secondary to HIV
Lymphomas (peripheral and CNS)
When should patients receive prophylactic TMP-SMX for Pneumocystis jirovecii carinii?
CD4 T-cell count < 200 or hx of oral candidiasis