Micro 11/17/08 1st hour Infections Associated to Immunodeficiencies, Clinical Correlation Dr.

Estrada Slide 1 This hour, were focusing on infections that you mainly see in immunodeficient pts. This lecture will be case-based. Slide 2 This is a child that presents with periorbital cellulitis. There is significant inflammation of the periorbital tissues. Then the child developed meningitis. He has been immunized appropriately (pneumonia, influenza, etc.). Because he has meningitis, there is a lumbar puncture performed. Slide 3 Here is a gram stain of the CSF. This is Gram (-) rod meningitis. In this case, it could be E. coli, but its not. We usually see this in infants at 1-2 months of age. This is Haemophilus influenza type B. It is very common worldwide. In this country, we dont see this that often anymore due to vaccination. Remember this baby had been immunized, so whenever you have this condition in a patient that was immunized, you have to think about immunodeficiency. This patient has a combined Ab deficiency. This is H. influenza meningitis. Skip to Slide 5 This is a 15-yo male with a history of cough and recurrent pneumonia. He has had multiple skin and soft tissue infections with S. aureus. He has an abnormal chest x-ray, so you do a BAL (broncheoalveolar lavage). This is a gram stain of the bronchial secretions. These are Gram (+) rods. There is a limited number of Gm (+) rods. Your differential for Gm (+) rods that can cause pneumonia would include C. diphtheria (but this pt doesnt have the symptoms of diphtheria), Listeria (usually affects very young babies or

older individuals, but it doesnt look filamentous like this picture does), Bacillus (anthrax), etc. Clostridium rarely causes pneumonia. This patient has Nocardia. Nocardia usually causes infections in immunocompromised people. It can cause localized cutaneous infections in immunocompetent people, but in general, a patient with Nocardia pneumonia will have an immunodeficiency. One primary immunodeficiency you would need to rule out here is Chronic Granulomatous Disease (CGD) because is a male and because he has also had chronic S. aureus infections. The treatment for this condition is Trimethoprim/Sulfamethoxazole. Back to Slide 4 This is a 4-yo presenting with fever and cough. He has had previous episodes of bacteremia caused by the same organism that is now causing the fever and cough. The chest x-ray shows consolidation in the right lung. When you see this, you have to suspect some type of bacterial pneumonia. This patient has bacteremia. The organism shown in the top picture is Streptococcus. These are Gm (+) diplococci. The type of Strep that is most likely diplococci is Streptococcus pneumoniae. This pt had a prior infection with this same organism. This is rather unusual. The immunodeficiency associated with these recurrent invasive infections with S. pneumoniae is a complement deficiency. This is easy to screen for. Also, you should consider an Ab deficiency. IgA is the most common Ab deficiency. You can easily test for these as well. Slide 6 This is just to remind you that CGD can be associated with unusual organisms, which in this case, caused abdominal abscesses. This one is caused by Candida. Skip to Slide 8 This is a child that has had recurrent infections caused by the same organism for the last two years. On this childs hand is a sore that has a dark area in it. This is necrotic tissue. If you see this in a recurrent fashion, you need to take a

biopsy. The lower picture is what you see on the biopsy. This is a fungal infection. This is a septated fungus. In a patient with a necrotic sore that shows a septated fungus, it is Aspergillus until proven otherwise. There are different species of Aspergillus. Aspergillus infections are usually a hallmark for people who are immunocompromised. People with recurrent Aspergillus infections should always be tested for immunodeficiencies (ex: CGD). An immunocompromised status can increase the chances of Aspergillus infection. One of the most common symptoms in a case like this is neutropenia. The treatment for this is debridement and antifungal meds. Slide 9 This is an 18-month old child that presents with a skin abscess. It is a large, red, indurated mass. The patient has had multiple draining boils in the past. On exam, the child is afebrile, has mild eczema, blue eyes, and a 3x4 cm abscess. His WBC and platelet count are normal. This is the 4th time this patient presents with a skin abscess during the last 6 months. You drain the abscess in your office. The gram stain of the material from the abscess is shown in the top picture. This is Staphylococcus, most likely S. aureus. These are Gm (+) cocci in clusters. This is probably the most common bacterial infection that you will see in your practice. What is not common is that this has been recurring, and the pt doesnt have a fever. He also has other conditions like eczema and blue eyes. This should raise a suspicion of Hyper-IgE syndrome, also known as JOB syndrome. Pts with recurrent S. aureus infections and eczema should be tested for Hyper-IgE syndrome. These pts tend to have IgE levels 10x higher than normal (1000 to 2000 range). They also have eosinophilia. Slide 10 This is a 20-month old presenting with fever and Gm (-) diplococci in the blood. This is his second infection with the same organism. He has petechial lesions initially. This is shown in the top picture. Eventually, it progressed to look like the bottom picture with necrotic tissue. He showed signs of sepsis and DIC. This is probably Neisseria meningitidis.

You will want to check for complement deficiency in this patient. There is a vaccine against meningococcal disease approved for children over age 11. Slide 11 This child presents at one month of age with this lesion on his mouth. This is the pts only problem. He has Candida. It is not uncommon to see Candida in young babies. This case does not require testing for immunodeficiency. This is a very common occurrence in children up to a month of age. What is unusual, though, is to see oral Candidiasis outside of the neonatal period (first month or so of life) or recurrent oral Candidiasis. In this case, you have to test for T-cell deficiencies. The most common one is HIV. Usually pts with HIV will also have Candida esophagitis. Slide 12 Normal infants usually do well with topical treatment for oral Candidiasis. We also see a large number of premature babies, and they are severely immunocompromised. This is a baby with skin cutaneous Candida infection. This is an invasive Candida infection that requires IV AB treatment. You want to diagnose Candida infections in premature babies ASAP because by the time it gets to this point, theres a very poor prognosis. Slide 13 This is a skin biopsy of a pt with severe disseminated Candidiasis. Slide 14 Another condition in which you can see severe Candida infections is chronic mucocutaneous Candidiasis. These pts develop a chronic Candidiasis of the skin and mucus membranes. Most of them do not have Candidemia where it involves the blood stream, but this is usually a chronic, indolent infection. Skip to Slide 16

This is one of my patients at 10-yo. His thrush, to this day, has never gone away, and he has now graduated from high school. We just control it with antifungals. He has also had skin involvement. We dont know why these pts dont get Candidemia. These pts tend to also have an autoimmune endocrinopathy. The outcome is not very favorable. Back to Slide 15 This is another picture of oral Candidiasis. Slide 17 Another organism that can cause problems in immunocompromised pts is cytomegalovirus. Neonates can develop CNS problems due to CMV infections during gestation if the mother is CMV nave. These babies have what we call blueberry muffin syndrome. They are yellow because of jaundice and have purple lesions on the skin from extramedullary hematopoiesis. This CT scan shows multiple calcifications in the ventricles of the brain. This is characteristic for CMV. The calcifications are in the ventricles. CMV can also cause problems in immunocompromised pts. Slide 18 One of the complications of CMV in addition to CNS problems is retinitis and resulting blindness. An ophthalmological exam should be done in any CMV pt to rule this out. This picture shows CMV retinitis. There are drugs we can use to treat CMV. Slide 19 This is a 7-month old boy with hypoxemia and tachypnea. His O2 saturation is only about 80%, and he is cyanotic. He has a congenital heart defect and low calcium levels. This xray shows hyperinflation with some infiltrate. BAL shows the organism stained with a silver stain. With this pts history, you should be concerned about DiGeorge syndrome. This is a pt with potential T-cell dysfunction. The organism shown in this BAL is Pneumocystis jiroveci, previously known as P.

carinii. This is seen in immunocompromised patients with Tcell deficiencies. Prophylaxis helps to prevent these infections, so immunocompromised pts should be put on trimethoprim-sulfamethoxazole prophylaxis. The treatment of choice is IV trimethoprim-sulfamethoxazole 3 times a week then prophylaxis for life. These pts rarely have bacteremia and fever. Note that the x-ray shows a more diffuse hyperinfiltrate. Slide 21 Tuberculosis can happen in immunocompetent and immunocompromised individuals. Pts with HIV are at high risk. Young children are at a much higher risk of getting the disease (if they are exposed) than adults are. The top picture shows a positive PPD. With this test, you measure induration (how hard it feels); you dont measure redness. This test tells you that the pt has been exposed to TB. Induration of >15mm diameter in an immunocompetent pt tells you that the pt has been exposed, and a measurement of just 5mm in an immunocompromised pt is considered positive. So its important to know if your pt is immunocompromised or immunocompetent. Slide 21 Toxoplasma is common in immunocompromised pts with advanced T-cell dysfunction. Toxoplasmosis is usually seen in HIV pts when their CD4 count is less than 100. It usually presents with CNS manifestations. This is a CT scan of a baby with a CNS Toxoplasma infection and hydrocephalus. The infection is causing an obstruction of flow of CSF. Slide 23 Molluscum contagiosum is a skin disease cause by a pox virus. The classic presentation is papular lesions with this umbilicated characteristic. If the infection only happens once, you shouldnt be too concerned about immunodeficiency. The problem is when it doesnt go away or when it is recurrent. Something that can mimic Molluscum contagiosum is skin streptococcal disease.

Slide 24 Cryptococcus is a skin disease, but it can also cause a CNS infection. The test you do is a streptococcal Ag test to the CSF or you can stain with india ink. Cryptosporidium parvum doesnt cause CNS disease, but it causes GI problems in immunocompromised pts. They have diarrhea that is difficult to treat. Slide 25 Pts with HIV are at risk of many clinical manifestations. HIV per se can cause many direct problems. One of those is HIV myocarditis. The virus itself can cause inflammation of the myocardium, which can lead to heart failure. Opportunistic infections can also occur. This can cause brain atrophy and dementia. This (top right) is a pt with Molluscum contagiosum. The bottom right picture shows oral leukoplakia, and the bottom left picture shows CMV retinitis. Slide 26 HIV can also cause wasting syndrome (top left). They are hypermetabolic. This pt (top right) has numerous ringworms. Usually these lesions in immunocompetent pts are single lesions that are easily treated. When you see multiple lesions, think about immunodeficiency. If you see multiple warts (bottom left), you have to suspect the possibility of Tcell dysfunction. Another thing that can happen is parotitis (bottom right). The presentation is similar to mumps. Slide 27 There is also a risk of developing chronic atypical mycobacterium infections with chronic granulations in the cervical area. They can also develop recurrent HSV infections (top right) or recurrent shingles (bottom picture). Slide 28 There is also a risk of Kaposis sarcoma, which is associated with HHV-8 infection. Slide 29

This is another picture of Kaposis. Slide 30 Pseudomonas aeruginosa is important in immunocompromised pts, especially those that are neutropenic or undergoing chemotherapy. Sometimes you can see ecthyma gangrenosum, shown in the bottom picture. There are dark areas in the skin. If you see this, check for the organism and start ABs ASAP. Slide 31 Neutropenia is a significant risk factor for Aspergillus infection. This is a dark scar with necrotic tissue. Try to take this tissue out. Even with anti-fungal therapy, its important to remove the tissue. Slide 32 Exposure to Varicella is important in immunocompromised pts. Most of us have either been infected with Varicella or seen a case of chicken pox in our lifetimes. However, you wont see it much in your career due to the vaccine. But, you will see this in immunocompromised patients. These pts can get really sick and possibly die due to the infection. If you suspect Varicella in an immunocompromised pt, start IV ABs right away. Slide 33 Once youve had Varicella, you are always at risk of developing shingles. These manifest as vesicular lesions on a particular dermatomal region. If you see this, its shingles until proven otherwise. Many people will have a tingling sensation in the area a couple days before the painful lesions appear. You usually see this in elderly individuals, but you can see it in immunocompromised children as well. If you see recurrent shingles infections in a child, you should suspect immunodeficiency. (He gives an example of a 15-yo child that had been hospitalized 8 times for shingles and never tested. The child ended up having HIV, and his CD4

count was in the single digits. He is now in college and is doing well.) Slide 16 This is another picture of Varicella. You can see lesions in different stages simultaneously. They will rupture and become scabbed. If the lesions are not scabbed, do not expose immunocompromised pts to the infected pt. Slide 17 There are different types of transplants. Depending on the type of transplant, you will have different types of infectious processes. Dont memorize which infections happen when, but just know that different infections happen at different times, depending on the type of transplant.