Funga l Infections in PIDD Patients PIDD patients are more prone to certain types of infections. Knowing which ones they are most susceptible to and how they are most commonly treated can help to minimize the risk. By Alexandra F. Freeman, MD, and Anahita Agharahimi, MSN, CRNP 16 December-January 2014 www.IGLiving.com IG Living! ndividuals with primary immune deficiencies (PID Ds) are (paronychia) or the finger nails and toenails themselves at greater risk for recurrent infections compared with (onychomycosis). Candida can enter the bloodstream and Ithose with normal immune systems. PIDD patients cause more severe infections when the normal skin barriers fre quently have a genetic defect that causes an abnormality are compromised such as with central venous access lines in the number and/or function of one or more compo - (long-term IV access) that are sometimes needed for various nents of the immune system that fights infections. These treatments. These invasive infections usually cause infections can be predominantly viral, bacterial or fungal, fever and more acute illness compared with the more depending on the type of white blood cells affected by the mild infections such as thrush and vaginal yeast infections. specific immune deficiency . For instance, neutrophil Ringworm is also caused by yeasts, including Trichophyton abnormalities lead to recurrent bacterial and mold infections ; and Microsporum species, that cause rashes on the skin or B lymphocytes typically lead to bacterial infections, more scalp. Tinea versicolor is caused by the yeast Malassezia specifically those that antibodies prevent such as furfur and causes a rash usually on the trunk. Streptococcus pneumoniae ( pneumococcus) and Haemophilus influenzae ; and T lymphocytes frequently lead to recurrent viral infections and yeast infections such as Candida. For medical purposes, Other types of immune system abnormalities lead to other specific recurrent infections. fungi are divided into three Individuals with PIDDs often require recurrent courses of antibiotics, which can lead to an imbalance in the normal groups: yeasts, molds and bacteria and fungi (normal flora) that inhabit all of our protective barriers such as the skin, gastrointestinal tract those that can exist as and oral mucosa. This imbalance, in turn, increases vulner - ability to other types of infections such as yeast infections and Clostridium difficile (C. diff) infections. both yeasts and molds What Are Fungi, and What Diseases (dimorphic fungi). Do They Cause? Fungi are categorized as eukaryotes, organisms whose Cryptococcus is a yeast that can be found in the soil, in cells are larger and more complex in their make up wild bird droppings and around certain plants. In healthy com pared with bacteria, which lack nuclei inside the cells, individuals, it rarely causes problems. However, in immune and viruses, which require assistance from host cells (the deficiencies with T lymphocyte abnormalities , it can usually cells it infects) to replicate. For medical purposes, fungi are cause lung infections when it is inhaled. The lung infection divided into three groups: yeasts, molds and those that can look like a mass on chest imaging scans but rarely can exist as both yeasts and molds (dimorphic fungi). causes many symptoms. However, Cryptococcus can Yeasts commonly include Candida species and Cryptococcus spread to the brain and cause meningitis. The meningitis species, with Candida being the more common. Candida symptoms may evolve over weeks to months, which is are a part of human normal flora and mostly reside in the dif ferent from bacterial meningitis, which rapidly causes mouth, gastrointestinal tract and vagina. Problems arise significant illness. This may present with symptoms such as when their numbers multiply in these areas due to the headaches, personality changes or vision changes. eradication of normal bacteria from antibiotic use, Molds are fungi that grow as multicellular organisms med ications like corticosteroids that weaken the immune that usually have branches called hyphae. The most common system, or when the improper function of the immune mold responsible for causing infections is Aspergillus. sys tem allows them to replicate unchecked. Candida can Aspergillus species grow in almost all oxygen-rich environ - cause infections in the mouth, known as thrush, which ments. It is rare for people with normal immune systems appear as white plaques on the inside of the cheeks and to have infection from mold, although breathing in high tongue. It can also cause vaginal yeast infections and quantities of molds can make asthma and other lung diseases dia per rash in infants and young children. And, it can worse. Problems with the neutrophil white blood cells, cause infections on the skin surrounding the fingernails either due to a PIDD (e.g. ,chronic granulomatous disease, December-January 2014 www.IGLiving.com IG Living! 17 Figure 1. plugs. Allergic fungal sinusitis causes thick mucous that often requires sinus surgery to clear. Both ABPA and aller gic fungal sinusitis improve typically with steroids such as prednisone. Dimorphic fungi that are mainly responsible for causing infections include Histoplasmosis, Blastomycosis and Coccidio idomycosis. Histoplasmosis is found in the soil mostly in the Ohio River Valley and lower Mississippi River area and usually causes a self-limited lung infection with a dry cough. Blastomycosis grows in moist or wet environments and vegetation and is found most fre - quently around the Great Lakes. Coccidio ides is found in This chest CT scan of a 23-year-old man with Hyper IgE syndrome shows a cavity in the right lung (thin red arrow) in which there is an aspergilloma the soil of primarily the Southwestern United States and (thick green arrow). Aspergillomas can cause hemoptysis (coughing up blood). causes valley fever, which is a flu-like illness with cough. All three can cause infections in individuals with normal Figure 2. immune systems, but the infections are not usually severe and frequently clear without any medications. Those with PIDDs can develop significant infection affecting the respiratory, neurologic and dermatologic systems from these organisms. What PIDDs Lead to Fungal Infections? As mentioned earlier , individuals with PIDDs have increased risk for certain fungal infections, and the type of PIDD determines the susceptibility to the infection and the severity of illness. CGD is caused by a problem in the neutrophil oxidative burst, which is the chemical end product of neutrophil activity that kills certain bacteria and fungi. This abnor - mal killing ability of neutrophils leads to susceptibility to This individual has a primary immunodeficiency (Hyper IgE syndrome) that leads to recurrent Candida infections. The arrow points to a nail that was infections with molds, most commonly with the infected with Candida. Aspergillus species . These mold infections are usually of the lung, skin or bone and can cause fever and some - times localizing symptoms to the site of infection. or CGD) or to chemotherapy, can cause severe mold Diagnosis is best made by taking a biopsy and sending infec tions that require long-term antifungals and possibly the sample for fungal and bacterial cultures so that surgery to cure. In CGD, pneumonias from molds can spe cific treatment can be given. cause chest pain, cough and fever and may worsen slowly Severe combined immune deficiency (SCID) is caused by over weeks compared with bacterial infections that usually severe abnormalities in T lymphocytes along with B and/or cause more symptoms rapidly. Molds can cause less severe, NK lymphocytes. Affected individuals present early in life but still problematic, chronic pulmonary infections in as infants with recurrent, severe bacterial and viral infec - indi viduals with bronchiectasis (irreversible dilation of tions , as well as failure to grow normally. Lymphocytes are part [s] of the bronchial tubes) or other structural lung also important for the control of yeasts , and infants with problems. People with asthma or cystic fibrosis can develop SCID frequently have yeast infections causing thrush and an allergy to molds and have allergic sinus or lung disease, diaper rash. known as allergic bronchopulmonary aspergillosis (ABPA) Hyper IgE (Job’s) syndrome is caused by mutations in a or allergic fungal sinusitis. ABPA normal ly causes wheezing gene called STAT3, which is needed for T lymphocytes to and productive cough with usually brown-colored mucous mature into a special type of T lymphocyte called a Th17 18 December-January 2014 www.IGLiving.com IG Living! cell. Th17 cells are involved in the control of yeast on the Polyene Antifungals: skin and mucous membranes , and individuals with • Nysta tin is used topically to treat thrush or skin infection s abnormal Th17 cells can have trouble with Candida in with Candida. With thrush, it is usually administered as a the mouth (thrush) , as well as fingernail Candida swish and spit. Side effects are rare. infections and recurrent vaginal yeast infections. Less • Amphotericin has activity against many fungi and is frequently, there can be more severe infections from used frequently for severe infections. Amphotericin use is Cryptococcus, Histoplasmosis, and Coccidio ides. These limited due to its intravenous administration and risk for can cause gas trointestinal infections and, in the case of kidney toxicity. Cryptococcus and Coccidio ides, can cause meningitis. Azole Antifungals: • Miconazole/clotrimazole are topical