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General: Symptoms vary depending on the specific OI associated with IRIS. In general, inflammatory signs that the immune system is functioning usually include fever, swelling and redness at the site of injury or infection, thick drainage and discharge at the site of infection and warmth and pain at the infection site. Below are some of the most common OIs that occur in IRIS patients. Cryptococcal meningitis: Cryptococcal meningitis is an infection of the meninges (membranes that surround the brain and spinal cord) caused by the fungus Cryptococcus neoformans. Symptoms usually include fever, headache, enlarged lymph nodes, blurred vision, sensitivity to light, stiff neck, seizures, confusion, behavior or mood changes, coma, nausea and vomiting. Onset of the infection has been reported between one week and 11 months after initiating ART. Cytomegalovirus (CMV): Cytomegalovirus (CMV) is a common viral infection that is related to herpes. The infection is usually a late complication, occurring about three years after HIV patients begin ART. Cytomegalovirus may affect one eye at first, but usually progresses to both eyes. Common symptoms include floaters (seeing spots or spider webs), light flashes, blind spots, blurred vision, obstructed areas of vision, photophobia (abnormal sensitivity to light) and sudden decrease of vision. Symptoms worsen as the patient's ability to fight off the infection decreases. In about 30% of cases there is evidence of retinal damage. Mycobacterium avium complex (MAC): Mycobacterium avium complex (MAC), or mycobacterium avium intracellulare (MAI), is a bacterial infection that is caused by either Mycobacterium avium or Mycobacterium intracellulare. MAC can be mild and localized or it can be severe, requiring systemic anti–inflammatory therapy, in addition to anti–MAC (antibiotic) therapy. Enlarged lymph nodes and fever are the characteristic symptoms of MAC. Other symptoms may include high fever, drenching sweats, diarrhea, weight loss, abdominal pain, fatigue, weakness, anemia (low levels of red blood cells), neutropenia (low levels of white blood cells), thrombocytopenia (low levels of platelets), blood infections, viral hepatitis (liver infection), skin lesions, pneumonia and elevated liver function tests. The liver or spleen may be enlarged. Tuberculosis (TB): Tuberculosis (TB) is a bacterial infection of the lungs, which is caused by the microorganism Mycobacterium tuberculosis. In an HIV patient who is receiving therapy for active TB, the onset of TB IRS typically occurs one to six weeks after the initiation of ART. The signs and symptoms of tuberculosis (TB) may include high fevers, lymphadenopathy (enlarged lymph nodes), worsening of pulmonary symptoms and infiltrates and pleural effusions. Non–pulmonary symptoms may include expanding central nervous system lesions, skin or visceral abscesses, bone lesions or hypercalcemia (high levels of calcium in the blood). Pneumocystis jiroveci pneumonia: Pneumocystis jiroveci pneumonia (formerly called Pneumocystis carinii pneumonia) is the most common opportunistic infection that occurs in HIV patients. Originally, researchers thought a one–cell organism (protozoan) called Pneumocystis carinii caused the disease, but recent research suggests that is a fungus called Pneumocystis jiroveci. The disease almost always affects the lungs, causing a type of pneumonia. The first signs of PCP are difficulty breathing, fever and a dry cough. Symptoms may include shortness of breath (especially after physical activity), fever, nonproductive cough, chest discomfort, weight loss, chills, hemoptysis (spitting up blood), tachypnea (rapid breathing), tachycardia (fast heart rate), mild crackles (bubbling, or rattling sounds that occur when air moves through fluid–filled airways), cyanosis (bluish discoloration of the skin), nasal flaring and intercostals retractions (visible use of muscles between the ribs, which indicates labored breathing). If IRIS occurs in patients with Pneumocystis jiroveci pneumonia, severe acute respiratory failure may result.
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