Histoplasmosis – Risk factors, Symptoms, and Diagnosis.

Overview

Histoplasmosis is an infection caused by breathing in spores of a fungus often found in bird and bat droppings. People usually get it from breathing in these spores when they become airborne during demolition or cleanup projects.

Soil contaminated by bird or bat droppings also can spread histoplasmosis, putting farmers and landscapers at a higher risk of the disease. In the United States, histoplasmosis commonly occurs in the Mississippi and Ohio River valleys. But it can occur in other areas, too. It also occurs in Africa, Asia, Australia, and in parts of Central and South America.

Most people with histoplasmosis never develop symptoms and aren’t aware they’re infected. But for some people — mainly infants and those with weakened immune systems — histoplasmosis can be serious. Treatments are available for even the most severe forms of histoplasmosis.

What Causes It?

Fungal spores can be released into the air when contaminated soil or droppings are disturbed. Breathing the spores may lead to an infection.

The spores that cause this condition are commonly found in places where birds and bats have roosted, such as:

• Caves
• Chicken coops
• Parks
• Older barns

You can get histoplasmosis more than once. However, the first infection is generally the most severe.

The fungus doesn’t spread from one person to another and it’s not contagious.

Risk factors

The chances of developing histoplasmosis symptoms increase with the number of spores you inhale. People more likely to be exposed include:

• Farmers
• Pest control workers
• Poultry keepers
• Construction workers
• Roofers
• Landscapers and gardeners
• Cave explorers
• Demolition workers

Most at risk of severe infection

Children younger than age 2 and adults age 55 and older have weaker immune systems. Because of this, they’re more likely to develop disseminated histoplasmosis — the most serious form of the disease. Other factors that can weaken your immune system include:

• HIV or AIDS
• Cancer chemotherapy
• Corticosteroid drugs, such as prednisone
• Tumor necrosis factor inhibitors, often used to control rheumatoid arthritis
• Medications that prevent rejection of organ transplants

Pathophysiology

H capsulatum in the saprobic state grows in the mycelial form. Macroconidia and microconidia are produced on the hyphae of mycelium and are converted to the yeast form under temperature-controlled regulation. The aerosolization of conidia and mycelial fragments from contaminated soil results in alveolar deposition via inhalation.

The host defense includes the fungistatic properties of neutrophils and macrophages. T lymphocytes are crucial in limiting the extent of infection. Susceptibility to dissemination is increased markedly with impaired cellular host defenses.

Conversion from the mycelial to the pathogenic yeast form occurs intracellularly. After phagocytosis by macrophages, the yeast replicates in approximately 15-18 hours. Despite fusion with lysosomes, multiplication continues within the phagosomes. Proposed theories suggest that the yeasts may produce proteins that inhibit the activity of lysosomal proteases.

As the host immunity response develops, yeast growth ceases within 1-2 weeks after exposure. Cytokines systemically activate the fungistatic activity of macrophages against intracellular yeasts. With further maturation of the cell-mediated response, delayed-type hypersensitivity to histoplasmal antigens occurs (3-6 wk after exposure). Approximately 85-90% of individuals who are immunocompetent produce a positive response to skin antigen test for Histoplasma species. Over weeks to months, the inflammatory response produces calcified fibrinous granulomas with areas of caseous necrosis.

Clinical manifestations of histoplasmosis appear with continued exposure to large inocula. The initial pulmonary infection may disseminate systemically, with hematogenous spread, and produce extrapulmonary manifestations. Hematogenous spread to regional lymph nodes may occur through the lymphatics or the liver and spleen. Progressive disseminated histoplasmosis is rare in adult hosts who are immunocompetent. Systemic spread usually occurs in patients with impaired cellular immunity and typically involves the CNS, liver, spleen, and rheumatologic, ocular, and hematologic systems.

Symptoms of Histoplasmosis

Most people have no symptoms, or only have a mild, flu-like illness.

If symptoms do occur, they may include:

• Fever and chills
• Cough and chest pain that gets worse when breathing in
• Joint pain
• Mouth sores
• Red skin bumps, most often on the lower legs

The infection may be active for a short period of time, and then the symptoms go away. Sometimes, the lung infection may become chronic. Symptoms include:

• Chest pain and shortness of breath
• Cough, possibly coughing up blood
• Fever and sweating

In a small number of people, especially in those with a weakened immune system, histoplasmosis spreads throughout the body. This is called disseminated histoplasmosis. In response to the infection irritation and swelling (inflammation) occur. Symptoms may include:

• Chest pain from inflammation of the sac-like covering around the heart (pericarditis)
• Headache and neck stiffness from swelling of the membranes covering of the brain and spinal cord (meningitis)
• High fever

Complications

Histoplasmosis can cause many serious complications, even in otherwise healthy people. For infants, older adults and people with weakened immune systems, the potential problems are often life-threatening.

Complications can include:

• Acute respiratory distress syndrome. Histoplasmosis can damage lungs to the point that the air sacs begin filling with fluid. This prevents good air exchange and can deplete the oxygen in your blood.
• Heart problems. Inflammation of the sac that surrounds your heart (pericardium) is called pericarditis. When the fluid in this sac increases, it can interfere with the heart’s ability to pump blood.
• Adrenal insufficiency. Histoplasmosis can harm your adrenal glands, which produce hormones that give instructions to virtually every organ and tissue in your body.
• In some cases, histoplasmosis can cause this inflammation of the membranes surrounding your brain and spinal cord.

Histoplasmosis Diagnosis

Your ophthalmologist will examine your eyes to confirm a histoplasmosis diagnosis. They will be looking for two things in particular:

• Histo spots
• Swelling of the retina, which signals the growth of new blood vessels that are not normal

Your doctor may have you use an Amsler grid to check for histoplasmosis symptoms such as wavy, blurry or dark areas in your vision.

Your ophthalmologist will dilate (widen) your pupils with eye drops. They will look at your retina and other areas in the back of the eye. Your ophthalmologist will look for fluid or blood vessels that are not normal. If you have these signs, your ophthalmologist will take special photographs of your eye. They use optical coherence tomography (OCT), OCT angiography, or fluorescein angiography to take these photographs.

OCT uses light waves to make detailed pictures of the area beneath the retina. OCT images show how thick the retina is. They can help your ophthalmologist find swelling and blood vessels that are not normal.

OCT angiography uses light waves to look at the blood vessels in the retina without needing a dye injection.

During fluorescein angiography, a dye is injected into a vein in your arm. The dye travels throughout the body, including your eyes. The dye highlights areas of the retina that are not normal.

Histoplasmosis Treatment

Anti-VEGF treatment

A certain chemical can cause blood vessels that are not normal to grow under the retina. This chemical is called vascular endothelial growth factor, or VEGF. One method for treating histoplasmosis is to block VEGF.

Several anti-VEGF drugs can block the trouble-causing VEGF. Blocking VEGF reduces the growth of blood vessels and slows their leakage. This helps to slow vision loss and in some cases improves vision.

Your ophthalmologist injects the anti-VEGF drug into your eye in an outpatient procedure. Before the procedure, your ophthalmologist will clean your eye to prevent infection. They will numb your eye with anesthetic eye drops. You may receive multiple anti-VEGF injections over the course of many months. Repeat anti-VEGF treatments are often needed for continued benefit.

Laser treatment

Laser treatment for histoplasmosis is usually done as an outpatient procedure. You will have this treatment either in the doctor’s office or at the hospital.

The laser beam in this procedure is a high-energy, focused beam of light. It produces a small burn when it hits the area of the retina where you need treatment. The burn destroys the blood vessels that are not normal. This prevents further leakage, bleeding and growth.

After laser treatment, your vision may be more blurry than before treatment. But this will often stabilize within a few weeks. A scar forms where the laser burned your retina. The scar makes a permanent blind spot that might be noticeable in your field of vision.

Laser treatment does not cure histoplasmosis. It reduces the chance of blood vessels spreading and causing more harm to your vision. If these blood vessels do return, you may need more laser surgery.

Steroid injection

Your ophthalmologist may treat you with steroid injections. These shots in the eye reduce swelling due to histoplasmosis.

Histoplasmosis remains a threat to your vision for your lifetime. It is important to have regular checkups with your ophthalmologist to detect any problems as early as possible.

• Colors lose their brightness; colors do not look the same for each eye
• Central light flashes or flickering

If you have any of the symptoms of histoplasmosis, you should see an ophthalmologist.

Is it possible to prevent Histoplasmosis?

There is no vaccine against histoplasmosis. In areas where the fungus is common, it may not be possible to prevent infection. Avoiding areas with bird and bat droppings may provide some protection. Wearing a respirator facemask can provide protection for workers in contaminated areas. Spraying soil with water before working the soil may help prevent release of spores into the air. Having had histoplasmosis in the past can offer some protection against severe disease if you become reinfected.

There are no commercially available tests to test for histoplasmosis in the environment, and people do not routinely carry out testing of soil and other environmental areas. Properly cleaning up bird or bat droppings, however, may help reduce the risk of contracting the infection.