CMV (retinitis, g.-i., CNS)

  • slide 48
  • Prof. Hirschel

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1/48 CMV and HIV

Reactivation of latent CMV infection can occur in advanced immune deficiency patients who have CD4 counts below 50. Retinitis, colitis and esophagitis are clearly recognized HIV-associated diseases. The existence of CMV encephalitis, and pneumonitis is controversial and often difficult to establish. While HAART has almost eliminated CMV disease, except for immune reconstitution syndrome shortly after starting treatment.

2/48 CMV retinitis (left), compared to a normal retina (right)

CMV retinitis (left), compared to a normal retina (right).

3/48 CMV Retinitis

Necrosis and inflammation; note typical peri-vascular sheathing

4/48 Initial lesions and later lesions

- The initial lesions are peri-vascular: "CMV vasculitis".- Later lesions show necrosis and hemorrhage.

5/48 Peripheral lesion of CMV retinitis. More centrally, cotton-wool exudates are also seen (arrows)

Peripheral lesion of CMV retinitis. More centrally, cotton-wool exudates are also seen (arrows).

6/48 A peripherally located lesion of CMV retinitis

A peripherally located lesion of CMV retinitis.

7/48 CMV retinitis

Resembling a pizza,note peri-vascular sheathing

8/48 CMV retinitis

Insert: vascular sheathing

9/48 3 peripheral lesions of CMV retinitis.

3 peripheral lesions of CMV retinitis.

10/48 Rapidly progressing CMV retinitis with loss of vision.

Rapidly progressing CMV retinitis with loss of vision.

11/48 Advanced immune deficiency=comorbidities

This patient was admitted to the ICU with respiratory failure due to disseminated histoplasmosis. When extubated, he complained of loss of vision (March 4, 2003). With ganciclovir treatment, he recoved most of his visual acuity (June 3, 2003).

12/48 CMV retinitis/vasculitis with vitreous inflammation

CMV retinitis/vasculitis with vitreous inflammation.

13/48 Differential diagnosis of CMV retinitis

Differential diagnosis of CMV retinitis.

14/48 CMV Retinitis: Differential diagnosis (1)

Benign « cotton wool » exudates in a HIV+ patient.

15/48 CMV Retinitis: Differential diagnosis (2)

Comparison between CMV retinitis (left), and benign exudates (right).

16/48 CMV Retinitis: Differential Diagnosis (3)

Differential diagnosis of CMV retinitis: Toxoplasmosis This patient was HIV-negative, and the lesion is shown before (left) and after treatment with sulfadiazine and pyrimethamine. When, as here, toxoplasma lesions are hemorrhagic, they resemble CMV

17/48 CMV Retinitis: Differential diagnosis (4)

Differential diagnosis of CMV retinitis: Toxoplasmosis. Marked edema and exudate in the vitreous body, resembles a "headlight in the fog".

18/48 CMV Retinitis: Differential diagnosis (5)

Retinal necrosis (this is not limited to HIV-related retinitis, but is occasionally seen in HIV- patients, due to herpes simplex, varicella zoster virus, or CMV)

19/48 CMV Retinitis: Differential diagnosis (7)

Retinal necrosis in disseminated virus infection. The line (arrows) delimits the retinal detachment.

20/48 CMV Retinitis: Differential diagnosis (8)

PORN: peripheral outer retinal necrosis. May be due to CMV, but virus is the most frequent cause in HIV infection.

21/48 CMV Retinitis: Differential diagnosis (9)

Miliary chorioretinitis, here due to tuberculosis. The differential includes candidemia, disseminated toxoplasmosis, PCP, and possibly syphilis.

22/48 CMV Retinitis: Differential diagnosis (10)

Chorioretinitis in a case of disseminated PCP. This patient was extremely immune suppressed, with less than 10 CD4 lymphocytes/μL. For prevention of PCP, he inhaled pentamidine monthly.

23/48 CMV Retinitis: Differential diagnosis (11)

Chorioretinitis due to syphilis.

24/48 CMV Retinitis: Differential diagnosis (12)

Chorioretinitis due to syphilis.

25/48 CMV Retinitis: Differential diagnosis (13)

Chorioretinitis due to . The patient had colon cancer, and was on long-term parenteral nutrition.

26/48 CMV Retinitis: Differential diagnosis (14)

Chorioretinitis due to .

27/48 CMV Retinitis: Differential diagnosis (14)

Chorioretinitis due to .

28/48 A case of CMV colitis

Immuno-deficient patient with diarrhea, tenesmus, abdominal pain, and fever. Note inflammed mucosa (left), and thickening of the walls of transverse and sigmoid colon, rectum, and bladder (arrows).

29/48 Stool from a baby with cytomegalovirus colitis

Stool from a baby with cytomegalovirus colitis

30/48 Colitis due to CMV

A seven month old baby, congenitally HIV-infected, with diarrhea. The images show mucus stool, and bright-red stool.

31/48 Colitis due to CMV

Histopathology reveals ulceration and inflammation with cytopathic cells suggestive of CMV (insert). The diagnosis is confirmed by antibody staining, specific for CMV (right).

32/48 CMV colitis; colonoscopy showing ulcers, bleeding, and pus

CMV colitis; colonoscopy showing ulcers, bleeding, and pus.

33/48 Longitudinal ulcers in a case of CMV esophagitis

Longitudinal ulcers in a case of CMV esophagitis

34/48 Multiple ulcers in a case of CMV esophagitis, 50 CD4 T cells/mm3

35/48 Typical longitudinal ulcers in a case of CMV esophagitis

Typical longitudinal ulcers in a case of CMV esophagitis. The lower part of the esophagus is seen, with the stomach to the right.

36/48 The prominent eosinophilic nucleolus in the submucosa of the esophagus is evidence for CMV infection

The prominent eosinophilic nucleolus in the submucosa of the esophagus is evidence for CMV infection.

37/48 Periventricular contrast enhancement suggestive of CMV encephalitis

Periventricular contrast enhancement is suggestive of CMV encephalitis (fine arrows), in a patient with a calcified lesion of cerebral toxoplasmosis (thick arrow).

38/48 Extensive CMV myelitis, 50 CD4 cells/mm3

39/48 Typical cytomegalic inclusions in a brain biopsy from a patient with AIDS

Typical cytomegalic inclusions in a brain biopsy from a patient with AIDS.

40/48 Brain biopsy stained with monoclonal antibodies against CMV

Brain biopsy stained with monoclonal antibodies against CMV.

41/48 CMV Infections: Treatment (1)

- All treatment for CMV are given at high doses for three weeks followed by dose reduction of 50 percent.- Treatment can be stopped once CD4 cells exceed 100 per μL.- Ganciclovir (Cymevene®)- per os: valganciclovir 2 x 900 mg/d for three weeks, then 900 mg/l- i.v. 5mg/kg/12 hr x 3 wks, then q24h- Adapt in case of renal failure- Essential side effect: leucopenia.

42/48 CMV Infection: Treatment (2)

- Foscarnet90 mg/kg i.v. q12 h x 3 weeks, then q 24h- adapter dose in case of renal function- administer after 2 L of NaCl 0.9%- essential toxicities: renal failure, hypocalcemia, anemia, nausea/vomiting, oral and genital ulceration.

43/48 CMV Infection: Treatment (3)

Cidofovir (Vistide®)5 mg/kg i.v. week 1,2,4,6,8 etc.- premedication with probenecide and hydration (NaCl: 0.9%)- Advantages: Convenient- Disadvantages: Renal toxicity, particularly if given with tenofovir or other potentially nephrotoxic drugs.

44/48 CMV Retinitis: Treatment (5)

Right eye: Pre-treatment; Post-treatment.

45/48 CMV Retinitis: Treatment (6)

Left eye: Pre-treatment; Post-treatment.

46/48 CMV Retinitis: Treatment (7)

Treatment of CMV retinitis: The peripheral lesion on the left is still active. On the right, after treatment with ganciclovir, pigment changes are still visible.

47/48 Cytomegalovirus retinitis

A. Whitening of the infected retina in the inferior half of the macula. B. One and a half years following treatment with intravenous and intravitreal ganciclover implant.

48/48 CMV Retinitis: Treatment (8)

CMV retinitis: Intra-ocular ganciclovir injection; Ganciclovir implant.

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