Primary Immunodeficiency Disease (PI)

Chronic medical conditions–like any form of primary immunodeficiency disease–can be frustrating to deal with and limiting in daily life. It’s only natural to want relief, but every treatment comes with valid concerns. Ohio Infusion Services understands and wants to keep you informed about your infusion treatment options. Together we can get you closer to feeling better.

What is Primary Immunodeficiency Disease (PI)?

Primary immunodeficiency disease (PI) is a general category that contains a wide array of illnesses that all involve a compromised or incomplete immune system. This means that an individual with a PI lacks inherent protection against infection. PI illnesses are genetic in nature, and are inherited from family members. They are often present at birth but may not become evident until early childhood or even adulthood and can affect an individual of any age, gender, or ethnicity.

Numbers vary, but PI may include anywhere from 300 to 450 or more individual immunodeficiencies, with more being regularly discovered. In every case, a patient lacks infection-fighting proteins in their blood called antibodies. Depending on which form of PI you have, general symptoms might include:

• Chronic infections in the skin, sinuses, throat, ears, lungs, brain, spinal cord, or the urinary or intestinal tracts
• Repeated infections that are unusual, severe, may require hospitalization, or will not clear up with standard treatment
• Swollen spleen, liver, or lymph node
• Inflammation of blood vessels
• Failure to thrive in an infant
• Chronic digestive problems (e.g., diarrhea)
• Various autoimmune conditions

If you and other members in your family all tend to have similar susceptibility to chronic, intense infections, there is a chance that you may be dealing with a PI. People with PI are generally more likely to deal with autoimmune disorders, blood disorders, and certain cancers. Early diagnosis via blood, skin, and genetic testing can expedite treatment and help to prevent long-term issues.

Types of Primary Immunodeficiency (PI)

There are hundreds of primary immunodeficiencies recognized by the International Union of Immunological Societies. Some of these are:

• Activated PI3K Delta Syndrome (APDS): Recurrent infections in the lungs, sinuses, and ears eventually lead to damaged bronchi and chronic breathing problems. Viral infections–such as Epstein-Barr–are also common, along with enlarged lymph nodes or masses of white blood cells.
• Agammaglobulinemia (X-Linked and Autosomal Recessive): Infections frequently occur at or near the surfaces of the mucus membranes in the ear, sinuses, lungs, and gastrointestinal tract, but can also involve the skin, bloodstream, and internal organs. Infections that would normally be overcome by immune response may be able to spread deep into bones, joints, or the brain.
• Autoimmune lymphoproliferative syndrome (ALPS): Levels of red blood cells, platelets, and white blood cells are very low, increasing the risk of infection and hemorrhage.
• APS-1 (APECED) Autoimmune polyglandular syndrome type 1 (APS-1): Also called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Causes autoimmunity against various organs and increased susceptibility to infection caused by Candida yeast.
• Ataxia Telangiectasia: Presents in childhood as an unsteady gait (ataxia), abnormal eye movements, and low fine motor control, all of which worsen with age. Speaking and swallowing are also typically affected. Abnormally shaped blood vessels cause discolored whites of the eyes and show up on sun-exposed skin.
• BENTA disease: High levels of certain immune cells cause an enlarged spleen, enlarged lymph nodes, and an elevated risk of lymphoma. Recurrent sinus and lung infections as well as other viruses are common.
• CARD9 Deficiency and Other Syndromes of Susceptibility to Candidiasis: Unique susceptibility to both localized and systemic, chronic infections caused by the yeast Candida.
• Caspase eight deficiency state (CEDS): Causes an enlarged spleen and lymph nodes and recurrent sinus, lung, viral infections, herpesvirus infections, and persistent warts.
• Chronic Granulomatous Disease (CGD): White blood cells are unable to kill certain bacteria and fungi, causing high susceptibility to serious or life-threatening infection. Potential for abscesses in lungs, liver, spleen, bones, or skin along with serious digestive, heart, kidney, or diabetic problems and inflammation.
• Chronic Neutropenia: A rare blood disorder resulting from low numbers of white blood cells for more than 3 months and causing increased susceptibility to bacterial and fungal infections. Can be congenital, acquired, or idiopathic.
• Common Variable Immune Deficiency (CVID): Causes frequent bacterial and viral infections in the upper airway, sinuses, and lungs, along with potentially acute lung infections that can lead to pneumonia or bronchiectasis. Could also cause diarrhea and other digestive issues, reduced liver function, an enlarged spleen and swollen glands or lymph nodes, along with painful and swollen joints and higher risk for some cancers.
• Complement Deficiencies: “Complement” describes a group of serum proteins that aid the body in fighting infection. Deficiencies can bring on recurring bacterial infections, autoimmune diseases, angioedema that doesn’t respond to treatment, renal disease and vasculitis.
• Congenital Agammaglobulinemia: Also known as X-linked agammaglobulinemia or Bruton's agammaglobulinemia, this immunodeficiency disease was the first ever identified, and is caused by a gene located on the X chromosome that does not allow for the production of antibodies. Children, especially boys, have congenital agammaglobulinemia, which leads to infections in the middle ear, sinuses, and lungs commonly, and in the bloodstream and internal organs less frequently.
• Congenital Athymia: Congenital athymia results when a child is born without a detectable thymus, the gland located on top of the heart that is responsible for the creation of infection-fighting T-cells. This causes severe immunodeficiency and immune dysregulation and can lead to life-threatening infections. Risks are greatest in the first two or three years of life.
• Congenital Neutropenia: This term refers to a group of syndromes and may also be referred to as congenital agranulocytosis, severe congenital neutropenia, severe infantile genetic neutropenia, infantile genetic agranulocytosis, or Kostmann disease. Low levels of a specific type of white blood cell (neutrophil) result in bacterial infections early in life, often on the skin, in the mouth, and in the lungs. 
• CTLA4 Deficiency: This is a rare genetic disorder in which mutations in a gene called CTLA4 negatively influence the production of a specific protein that usually slows down immune response. In CTLA4 patients, the immune system is disregulated and immune cells infiltrate into other bodily systems, causing intestinal disease, enlarged lymph nodes, liver, and spleen, and respiratory infections. The blood, thyroid, skin, and joints are commonly affected.
• DiGeorge Syndrome: More accurately called 22q11.2 deletion syndrome, this genetic disorder comes about when a small part of chromosome 22 is missing. The development of several body systems is affected, including heart defects, poor immune function, a cleft palate and other facial differences, low calcium, delayed development, and behavioral and emotional problems. While symptoms of this condition sometimes overlap with those of autism, they are distinct.
• DOCK8 Deficiency: Named for the altered gene responsible for the disease, DOCK8 deficiency leads to lower-than-normal numbers of immune cells that can move through dense tissue. Chronic or recurrent severe viral, bacterial, or fungal infections of the skin and respiratory system are common, as are eczema, food or environmental allergies, and asthma.
• GATA2 Deficiency: Also called GATA2 haploinsufficiency, this disorder of the immune system is characterized by serious problems in the blood, lungs, skin, and both the vascular and lymphatic systems. Blood and skin cancers are also possible, along with unusual infections and hearing loss.
• Glycosylation Disorders with Immunodeficiency: Also known as PGM3-CDG, a mutation in the PGM3 gene can disrupt normal glycosylation–the attachment of sugars to proteins–and thereby negatively affect the immune system. Immunodeficiency results, along with potentially extensive and severe symptoms, including recurrent infections in the lungs, ears, skin, or gastrointestinal tract, allergies of all kinds, asthma, eczema, autoimmunity, developmental delays, and skeletal abnormalities involving the ribs or bones in the hands, feet, or spine.
• Hemophagocytic Lymphohistiocytosis (HLH): This systemic inflammatory syndrome results from an intense activation of the immune system, sometimes inherited (primary or familial HLH), and sometimes in response to infection or cancer or other primary immune deficiencies (secondary HLH). Immune cells that normally attack bacteria and viruses become overactive and attack the body, sometimes in the blood and bone marrow, spleen, liver, lymph nodes, skin, and brain, among other sites. HLH is marked by a high and unrelenting fever, rash, hepatitis, jaundice, an enlarged liver and spleen, low blood cell counts, enlarged lymph nodes, and various neurological issues.
• Hyper-Immunoglobulin E Syndromes (HIES): Also commonly known as Hyper IgE Syndromes, this group of conditions, which each result in high levels of an antibody called immunoglobulin E (IgE), are paired with genetic changes that cause symptoms specific to the illness. Hyper IgE conditions include autosomal-dominant CARD11 deficiency, DOCK8 deficiency, IL6R deficiency, IL6ST deficiency, PGM3 deficiency, and STAT3 dominant-negative disease, among others.
• Hyper-immunoglobulin M (IgM) Syndromes: Hyper IgM Syndromes are caused by the failure of the immune system to produce certain antibodies needed for fighting infections, but elevated levels of IgM. This inherited condition is generally evident early in life, demonstrated as severe respiratory infections in infancy and a higher risk of rare infections and some types of cancer throughout life. Recurrent viral and bacterial upper and lower respiratory tract infections are also common, along with gastrointestinal issues, autoimmune disorders, neutropenia, and an enlarged spleen and lymph nodes.
• IgG Subclass Deficiency: The body makes five major types of immunoglobulins: A, G, M, D, and E. Immunoglobulin G (IgG) is the most common and it has four subclasses that aid in preventing infections and multiply to attack potential sources of infection. A deficiency in any of the IgG subclasses can present as recurrent ear, sinus, gastrointestinal, and respiratory infections in young children. IgG subclass deficiency may be linked to another immunoglobulin deficiency.
• Interferon Gamma, Interleukin 12 and Interleukin 23 Deficiencies: These rare, inherited immune disorders result from the body’s failure to produce one or more of these signaling molecules, which in turn do not allow immune cells to communicate and collaborate to fight infections. These deficiencies lead to an increased susceptibility to both bacterial and viral infections along with inflammatory lesions called granulomas which form in tissues and organs due to recurring infections.
• Innate Immune Defects: A healthy immune system has both innate and adaptive responses that aid in fighting infection. A defect in the innate immune response stunts the body’s otherwise naturally rapid and reliable response to infection, resulting in primary immunodeficiency diseases.
• Leukocyte Adhesion Deficiency (LAD): LAD is caused by a mutation in a specific gene and is a rare, inherited, immune disorder. Phagocyte immune cells aren’t able to fight off invading pathogens and prevent infection. This leads to recurrent, sometimes life-threatening infections and general poor wound healing. Soft-tissue infections, gum inflammation, and tooth loss are also common.
• LRBA Deficiency: LRBA deficiency is a rare genetic disorder that results from mutations in the LRBA gene. Immune system function is compromised, which causes autoimmunity, recurrent infections and an increased risk of lymphoma. Excessive numbers of other immune cells–lymphocytes–can accumulate in the gut, lungs and brain, causing a wide range of infections and diseases due to the immune system not being able to slow down.
• NEMO Deficiency Syndrome: NEMO, short for NF-kappa B Essential Modulator, is a protein in white blood cells that helps to signal infection to the body. Genetic mutations in NEMO lead to deficiency, and can manifest differently in each individual. Common symptoms include skin diseases and susceptibility to potentially severe infections that can affect almost any body part. NEMO occurs nearly exclusively in boys.
• PI3 Kinase Disease: Genetic changes that result in PI3 Kinase disease overactivate a central pathway used by the immune system. The normal development of infection-fighting B and T cells is interrupted, leading to a weakened immune system and frequent bacterial and viral infections. PI3 Kinase disease can lead to swollen lymph nodes and spleen, chronic Epstein-Barr virus, and an increased risk of developing lymphoma.
• PLCG2-associated Antibody Deficiency and Immune Dysregulation (PLAID): PLAID and diseases that mimic the symptoms of PLAID are rare immune disorders that feature an allergic response to cold. Resulting inflammation and rash, called cold urticaria, is the most common and distinct symptom and can be experienced from infancy. Individuals may also notice a burning sensation in the throat when eating cold foods. Recurrent bacterial infections and autoimmune symptoms can also happen, along with an increased likelihood of developing an autoimmune disorder.
• Selective IgA Deficiency: Of the five types of immunoglobulins (antibodies) that are traditionally found in the blood, individuals with Selective IgA Deficiency have no detectable levels of IgA, which is pivotal in protecting the body’s mucosal surfaces from infection. Selective IgA Deficiency is relatively common, with some individuals having no illness, and others developing a variety of clinical problems.
• Selective IgM Deficiency: Much like Selective IgA Deficiency, patients with Selective IgM Deficiency have low levels of a specific antibody, in this case IgM, present in their blood. The body’s response to this deficiency varies, with some presenting as asymptomatic, and others dealing with severe, recurrent infections. IgM deficiency can also be seen in conjunction with DOCK8 deficiency.
• Severe Combined Immune Deficiency (SCID) and Combined Immune Deficiency: SCID is a genetic disorder that an infant inherits and that negatively affects T cells, leaving them with a very weak, nearly non-functioning immune system. The little immune protection they may have is not enough to fight off even mild infections from bacteria, viruses, and fungi. A SCID patient has recurrent and chronic illness that can be life-threatening without appropriate treatment. 
• Specific Antibody Deficiency (SAD): SAD results from an acute lack of sufficient specific IgG antibodies, meaning that, while antibodies may be present, the individual has not developed the appropriate immune response necessary to make specific antibodies against the polysaccharide (sugar) coating on certain bacteria, leaving them unprotected. Individuals with a deficiency can experience recurring upper and lower respiratory infections if the other parts of their immune system are not mounting a robust response. 
• STAT3 dominant-negative disease (STAT3DN): STAT3 is also known as autosomal dominant hyper-IgE syndrome (AD-HIES), or Job’s Syndrome, is a rare genetic disorder. The condition is the result of mutations in the gene that regulate the STAT3 protein, resulting in very high levels of immunoglobulin E (IgE). Recurring infections of the skin and lungs, frequent bone fractures, unusually flexible joints, growth and development issues and inflamed skin are other common symptoms, along with swollen lymph nodes, low blood cell counts, and autoimmunity that affects multiple organs and tissues. 
• Transient Hypogammaglobulinemia of Infancy (THI): Babies typically do not need to create their own antibodies while in utero, however during the last trimester of pregnancy they will build an immunity equal to that of their mother. When born, an infant will also receive some antibodies from their mother’s milk. Starting at around 6 months of age, their initial immunity will have faded and their own immune system has begun to take over. If this does not happen and the baby continues to experience a low immune protection, they will be left unprotected and vulnerable to infectious diseases. THI occurs when an infant’s IgG levels are significantly lower than 97% of infants their age. Upper and lower respiratory tract infections, allergic symptoms, and gastrointestinal problems are common symptoms. Severe viral and bacterial infections are also possible.
• WHIM Syndrome (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis): WHIM is a rare genetic condition that prevents certain white blood cells from moving from the bone marrow into the bloodstream. This results in an immune deficiency, which presents as frequent bacterial and viral infections in the respiratory system, ears, and skin, and an increased risk for certain types of cancer. 
• Wiskott-Aldrich Syndrome (WAS): WAS is a rare genetic condition that results from a  mutation in the WAS gene that controls production of a specific protein. WIthout this protein, the body has a decreased ability to fight intruders and cannot properly form platelets. WAS causes an abnormal immune response and a reduction in the ability to form blood clots. Individuals with WAS can experience prolonged bleeding along with recurrent bacterial and fungal infections. They may also see an  increased risk of certain cancers, eczema, and other autoimmune diseases. WAS primarily affects boys, and the severity of the disease can vary widely, even in related individuals..
• X-Linked Agammaglobulinemia (XLA): XLA results from an inability to produce B cells, or immunoglobulins (antibodies), stemming from a mutated gene on the X chromosome. Individuals can develop frequent infections of the ears, throat, lungs, and sinuses, along with infections in the bloodstream, central nervous system, skin, and internal organs and chronic viral infections. XLA patients will also either lack tonsils or they will be small and underdeveloped.
• X-Linked Lymphoproliferative Disease (XLP): XLP is caused by mutations in a gene on the X chromosome that provides instructions for making a specific protein. This then leads to defects in T- and B-cell interactions, which causes abnormal immune responses and produces a lifelong vulnerability to Epstein-Barr virus (EBV) that can manifest as swollen lymph nodes, an enlarged liver and spleen, hepatitis and lymphoma when exposed to EBV. XLP primarily affects boys and individuals will generally be healthy until they are exposed to the EBV, though they are likely to have an overactive immune response to viral infection.
• XMEN Disease: This is a rare genetic disorder characterized by low levels of infection-fighting CD4+ cells which leads to chronic Epstein-Barr virus (EBV) infection and an EBV-related disease which prompts the immune systems to produce excessive numbers of immune cells. It manifests as combined immune deficiency.

Infusion Therapy and Other Treatments for Primary Immunodeficiency Disease (PI)

PI conditions impair the immune system’s ability to defend the body against bacteria, viruses, fungi, and cancer cells. As a result, unusual infections or cancers can develop. On top of this predisposition to illness, it has been found that up to 25% of individuals who have an immunodeficiency disorder may also have an autoimmune disorder, further compounding the cycle of disease. But all hope is not lost–there are many viable treatment options available.

Ohio Infusion Services offers a variety of biologic and immunotherapy treatments that can help individuals with an immunodeficiency or an autoimmune disease to better fight off infections and illness. If oral medications have not made a difference, infusion therapy can often help to support and strengthen a weakened immune system. 

We offer intravenous immunoglobulin (IVIg) treatment options for patients with PI. IVIg infusions are administered through a vein in your arm and have been proven to be safe, effective, reliable, and are generally well-tolerated. IVIg therapies currently offered at Ohio Infusion Services include:

• Bivigam
• Gammagard
• Gammaked
• Gamunex-C
• Octagam
• Panzyga
• Privigen

Some medications are best used for adults, while others are ideal for younger patients–get in touch with your physician and feel free to contact our knowledgeable team for more information regarding each treatment regime.

Side Effects of IVIg Treatment for Primary Immunodeficiency Disease (PI)

Every form of IVIg therapy carries risks. Even though available treatment options have been found to be safe in the majority of cases, medications can react differently in everyone's body. Common, mild side effects could include:

• Headache
• Chills
• Fever
• Flushing
• Flu-like muscle or joint pain
• Fatigue
• Nausea and/or vomiting
• Abdominal pain
• Skin rash
• Wheezing

It is relatively common for patients to experience side effects of IVIG therapy both during and after the infusion. Symptoms could last up to 48 hours afterwards, depending on various factors. If symptoms continue for more than 48 hours or worsen as time goes on, the safest course is to contact your healthcare provider. If side effects post-treatment become severe, a visit to the hospital may be in order. Serious allergic reactions or low blood counts are definitely reasons to seek immediate medical care.

What To Expect from IVIg Infusion Therapy for Primary Immunodeficiency Disease (PI)

Apart from the above-mentioned side effects to be aware of, PI patients who are undergoing IVIg treatment should have a discussion with their medical provider regarding what to expect. Depending on their condition, age, and medication dosage, the length of the treatment and intensity of any side effects could vary greatly. 

At Ohio Infusion Services, we understand that while you are dealing with treatment for an illness, comfort is important. You can rest assured that you will always receive premium care in our facilities. Your first treatment session is overseen by an on-site physician or nurse to ensure that your dosage is well tolerated. Subsequent therapies are administered in the privacy of your own suite, with trained medical staff nearby. We hope that your IVIg treatment will help your condition right away, but medications do generally take time to reach their full effect.

If Your Doctor Has Prescribed IVIg Infusion Therapy, Ohio Infusion Services Can Help

It’s easy to work with us and start on your path to better health. Once you and your doctor decide to proceed with IVIg therapy, we will need their referral, which can be submitted via our website. In the meantime, please take a moment to fill out a new patient form so we know you’re interested in pursuing treatment. We will reach out to discuss IVIg therapy with you, and once we have your insurance information on file we can order medication and start the scheduling process. 

Ohio Infusion Services partners with most common insurance providers and will work quickly to ensure that you can get started with treatment as soon as possible. We look forward to serving you Monday through Friday in our Mayfield Heights or North Olmsted location. Our friendly and knowledgeable staff work diligently to streamline treatment and help to get your healing underway. If you'd like to learn more or find out whether we can offer treatment for your specific condition, please call us at 216-381-3333–we’re here to help.