Combined immunodeficiency with impaired immunity to human herpes virus 8 is a very rare inherited immune system disease. [1] In this disease, the body cannot make a strong T-cell response against human herpesvirus 8 (HHV-8), a virus that can cause cancers such as Kaposi sarcoma. [2] Because the immune system is weak in this special way, a child may develop widespread Kaposi sarcoma and other HHV-8–related problems, even when they look otherwise healthy. [3] This condition is usually due to a fault (mutation) in a gene called TNFRSF4, which makes a protein named OX40 that helps T cells become fully active and remember infections. [2]
Combined immunodeficiency with impaired immunity to human herpesvirus 8 (HHV-8) is a very rare genetic disease where both T cells and B cells (two key white blood cells) do not work properly, because of changes in a gene such as OX40 (TNFRSF4).[1] In this condition, the body cannot make a strong, long-lasting immune response, especially against HHV-8, the virus that causes Kaposi sarcoma and some other blood and lymph-node cancers.[1][2] Children with this disease often develop aggressive, widespread Kaposi sarcoma affecting the skin, lymph nodes, and internal organs, as well as problems like low blood cell counts (pancytopenia), big spleen (splenomegaly), and repeated infections.[1][3] It is usually inherited in an autosomal recessive pattern, which means a child must receive one faulty copy of the gene from each parent.[1] Because this is an ultra-rare disorder, there is no single standard treatment; care is based on expert opinion, case reports, and treatment guidelines from related conditions such as primary immunodeficiency and HHV-8–associated Kaposi sarcoma.[2][4]
Other names
This disorder has several other names in the medical literature. [1] One common name is “combined immunodeficiency with impaired immunity to human herpesvirus 8”, which describes the main problem: both T and B cell function are affected, and the weakness is especially clear against HHV-8. [1] Another name is “combined immunodeficiency due to OX40 deficiency”, because the missing or faulty protein is OX40. [2] Doctors may also say “TNFRSF4 deficiency”, since TNFRSF4 is the gene that encodes OX40. [2] In reports of affected families, the disease has also been described as “inborn error of immunity predisposing to childhood-onset Kaposi sarcoma”, stressing that it is present from birth and increases the risk of early Kaposi sarcoma. [3][4]
Types
Doctors do not yet divide this rare disease into many formal subtypes, because only a small number of patients have been reported worldwide. [1] However, experts sometimes think about “types” based on how the disease looks in real life. [3]
Type 1 – Classic childhood-onset Kaposi sarcoma with OX40 deficiency: These patients develop Kaposi sarcoma in childhood, often with many skin spots and sometimes internal organ disease, but have few other infections. [3][4]
Type 2 – Combined immunodeficiency with broader infections plus Kaposi sarcoma: Some people may have more frequent or severe infections (for example, lung or gut infections) along with Kaposi sarcoma, because T-cell help for many responses is reduced. [5][6]
Type 3 – Latent or mild form with strong HHV-8 antibody response problems but little clinical disease (theoretical): Researchers think that some relatives may carry similar gene changes, have weak immunity to HHV-8, but never develop full Kaposi sarcoma, especially if they are not strongly exposed to the virus. [6][4]
These “types” are a simple way to describe patterns; they are not yet official categories, because more patients and more research are needed. [1][6]
Causes
Remember: the root cause is genetic, but many other factors can trigger or worsen disease. [1][6]
TNFRSF4 (OX40) gene mutation – A change (mutation) in both copies of the TNFRSF4 gene stops the body from making normal OX40 protein on activated T cells. [2][3] Without OX40, T cells cannot fully grow, survive, and remember HHV-8, so the virus is not controlled well. [3][6][1]
Autosomal recessive inheritance – The disease usually happens when a child receives one faulty TNFRSF4 gene from each parent. [1][2] The parents are often healthy carriers with one normal and one faulty copy. [2]
Inborn error of immunity to HHV-8 – This disorder is part of a group called “inborn errors of immunity to oncogenic viruses,” meaning an immune pathway is broken from birth and this allows certain cancer-causing viruses to escape control. [5][6]
Defective T-cell co-stimulation – OX40 is a co-stimulatory receptor on activated T cells; if it does not work, T cells receive weaker “second signals,” so they do not expand and persist properly after HHV-8 infection. [3][6]
Poor memory T-cell formation – OX40 helps create long-lived memory T cells. [3] Without it, the body cannot “remember” HHV-8 well, so the virus can come back or stay active and drive tumors such as Kaposi sarcoma. [3][5]
Impaired control of HHV-8–infected endothelial cells – HHV-8 infects blood vessel lining cells and lymphatic endothelial cells. [5] When T-cell control is weak, these cells can grow in an abnormal way and form Kaposi sarcoma lesions. [3][5]
Impaired control of HHV-8–infected B cells – HHV-8 also infects B lymphocytes, which can give rise to lymphoproliferative diseases and lymphomas. [5][10] With defective OX40 signaling, B-cell responses and helper T-cell support are less effective, increasing the risk of HHV-8–related lymphoid disease. [5][10]
High environmental exposure to HHV-8 – In some regions, HHV-8 infection is common in childhood. [5][34] A child with OX40 deficiency who lives in such a region has a higher chance of early and repeated exposure, which can trigger Kaposi sarcoma. [4][34]
Family consanguinity (parents related by blood) – In reported families, parents may be related (for example, cousins), which increases the chance that both carry the same rare TNFRSF4 mutation and have affected children. [3][16]
Coexisting minor immune variations – Some family members may carry other mild immune gene differences that, together with OX40 deficiency, further weaken anti-HHV-8 defenses, although this is still under study. [5][6]
Chronic inflammation – Long-lasting inflammation due to other infections or autoimmune problems may create a “fertile ground” for HHV-8 to drive tumor growth, especially when antiviral immunity is weak. [5][6]
Co-infection with HIV (rare combination) – In theory, having both OX40 deficiency and HIV infection would cause very deep T-cell failure, greatly increasing the risk of severe HHV-8 disease; HIV alone already raises HHV-8 tumor risk. [17][7]
Use of strong immunosuppressive drugs – Medicines such as high-dose steroids or chemotherapy can further weaken an already impaired immune system, allowing HHV-8 to reactivate and drive tumor growth. [7][29]
Malnutrition – Poor nutrition can damage immune function in any person. [6] In a child with OX40 deficiency, malnutrition may make HHV-8 control even worse and speed up disease. [4]
Chronic stress and poor general health – Severe, long-term stress and unmanaged chronic diseases can reduce immune responses and make HHV-8 infection harder to control in someone with an underlying immune defect. [6]
Delayed diagnosis – Because this condition is extremely rare, doctors may not suspect it early. [1] Late diagnosis means that HHV-8 can act unchecked for many years, leading to more advanced Kaposi sarcoma. [3][4]
Lack of access to specialized care – In areas without immunology or genetics services, children at risk may not receive proper testing, counseling, or antiviral treatments, which worsens outcomes. [4][6]
Unprotected contact with HHV-8 sources – HHV-8 can spread via saliva, sexual contact, and sometimes blood products. [5][29] People with this immunodeficiency may be more strongly affected by such exposures. [5]
Co-infection with other herpesviruses – Other herpesviruses such as EBV or CMV can also stress the immune system and might indirectly make HHV-8 disease more likely or more severe in this setting. [5][29]
Genetic background and ethnicity – Certain families and populations seem to have higher HHV-8 exposure and possibly different genetic backgrounds that interact with TNFRSF4 mutations to affect disease risk, though this is still being studied. [4][34][6]
Symptoms
Not every patient has all symptoms, and published cases are few, but these are typical or possible features. [1][3]
Skin lesions of Kaposi sarcoma – The most common sign is purple, red, or brown spots or nodules on the skin, often on the legs, face, or trunk. [3][4] These lesions are made from abnormal growth of HHV-8–infected blood vessel cells. [5]
Mucosal lesions (mouth, nose, throat) – Raised or flat purple lesions can occur on the gums, palate, or inside the nose and throat, which may bleed or feel sore. [3][5]
Swollen lymph nodes – Lymph nodes in the neck, armpit, or groin may enlarge because HHV-8 infects immune cells inside them and drives overgrowth. [4][5]
Fever – Some patients have recurrent or long-lasting fevers without a clear bacterial cause, due to chronic viral activity and inflammation from HHV-8–related disease. [5][17]
Unexplained weight loss – Persistent infection and chronic inflammation can reduce appetite and increase energy use, leading to weight loss in children and adults. [4][5]
Night sweats and fatigue – Children may wake soaked in sweat and feel very tired during the day, due to ongoing immune activation against uncontrolled HHV-8. [5][17]
Shortness of breath or cough – If Kaposi sarcoma involves the lungs or airways, patients can develop cough, breathlessness, or chest discomfort. [7][3]
Abdominal pain or swelling – Involvement of the digestive tract or abdominal lymph nodes can cause pain, swelling, or a feeling of fullness. [4][5]
Gastrointestinal bleeding – If lesions form in the stomach or intestines, there may be black stools, blood in stool, or anemia from slow blood loss. [4][7]
Edema (swelling of legs or face) – Kaposi lesions in lymphatic vessels can block drainage and cause swelling of the legs, feet, or face. [3][5]
Recurrent mild infections – Some people may have more frequent colds, bronchitis, or other infections compared with healthy peers, because T- and B-cell cooperation is not ideal. [2][6]
Enlarged spleen or liver – Chronic viral infection and immune activation can enlarge the spleen or liver, which may be felt as a mass or heaviness in the upper abdomen. [4][5]
Anemia and low blood counts – Chronic disease or gastrointestinal bleeding can cause low red blood cells, and in some cases HHV-8–related conditions can disturb marrow function. [5][10]
Lymphoma-like symptoms – Very rarely, patients may develop HHV-8–associated lymphomas, with severe fatigue, rapid weight loss, drenching night sweats, and very large lymph nodes. [5][10]
Psychological distress – Visible skin lesions, chronic illness, and fear about cancer can cause anxiety, sadness, or social withdrawal, especially in children and teenagers. [4][6]
Diagnostic tests
Doctors use a mix of physical exam, simple bedside tests, laboratory and pathology tests, electrodiagnostic studies in selected cases, and imaging. [1][2][7]
Physical exam tests
Full skin examination – The doctor carefully looks at the whole skin surface, including scalp, mouth, and genital area, to find purple or brown spots, nodules, or plaques that suggest Kaposi sarcoma. [3][4] The number, size, and pattern help decide how advanced the disease is. [3]
Lymph node examination – The neck, armpits, groin, and other regions are felt for enlarged, firm, or tender lymph nodes. [4] This can point to HHV-8–driven lymphoproliferation or lymphoma, and guides further testing. [5][10]
Abdominal palpation – The doctor feels the abdomen to check liver and spleen size, tenderness, and masses. [4] An enlarged liver or spleen suggests chronic infection, portal hypertension, or organ involvement by Kaposi sarcoma or lymphoma. [5]
Respiratory and cardiovascular exam – Listening to the lungs and heart can detect fluid, crackles, or other sounds that might suggest lung involvement, heart failure, or anemia due to chronic disease. [7][5]
Manual / bedside tests
Performance status and growth assessment – Simple scores for activity level and checks of weight, height, and growth curves help show the overall impact of chronic HHV-8 disease and immune deficiency on daily life and development. [4][6]
Capillary refill and skin turgor test – Pressing on the nail bed or skin to see how quickly color returns can show dehydration or poor circulation, which may result from bleeding, anemia, or heart strain related to advanced disease. [4][7]
Stool occult blood test (bedside card test) – A small stool sample is tested with a chemical kit to detect hidden blood. [7] This is useful if gastrointestinal Kaposi sarcoma is suspected but bleeding is not visible. [4]
Simple neurological bedside exam – Checking strength, sensation, reflexes, and basic coordination can screen for nervous system involvement or side effects of treatments such as chemotherapy or antivirals. [7][17]
Laboratory and pathological tests
Complete blood count (CBC) – This test looks at red cells, white cells, and platelets. [5] It can show anemia from chronic disease or bleeding, low platelets from marrow involvement, or other changes that guide further study. [5][10]
Inflammatory markers (ESR, CRP) – These blood tests show general inflammation. [5] High levels may support the presence of active infection, chronic inflammatory activity, or HHV-8–related systemic disease. [5][17]
Immunoglobulin levels and lymphocyte subsets – Measuring IgG, IgA, IgM and counting T-cell, B-cell, and NK-cell numbers give a picture of basic immune status and help distinguish this disease from other combined immunodeficiencies. [2][6]
Functional T-cell assays (proliferation tests) – In specialized labs, T cells from the patient are stimulated in vitro and their growth and cytokine production are measured. [6] In OX40 deficiency, certain activation and memory responses can be reduced. [3][6]
HHV-8 serology (antibody tests) – Blood tests can look for antibodies against HHV-8. [5] Many patients with Kaposi sarcoma and immunodeficiency will have evidence of past or current HHV-8 infection. [5][33]
HHV-8 PCR (viral DNA detection) – A very sensitive test that detects HHV-8 DNA in blood, tissue, or body fluids. [5] High or persistent viral loads suggest uncontrolled infection and can help monitor treatment. [5][17]
Biopsy of skin or lymph node lesions – A small piece of tissue from a lesion is taken under local anesthesia and examined under a microscope. [3][4] Typical Kaposi sarcoma shows spindle cells and abnormal blood vessels; special stains can show HHV-8 proteins. [3][9]
Immunohistochemistry for HHV-8 LANA – On biopsy samples, staining for the HHV-8 latency-associated nuclear antigen (LANA) confirms that cells in the lesion are infected by HHV-8. [5][9] This is a key step in diagnosing HHV-8–associated tumors. [5]
Genetic testing for TNFRSF4 (OX40) – Sequencing of the TNFRSF4 gene identifies mutations that cause OX40 deficiency. [2][3] Showing two disease-causing changes confirms the inherited combined immunodeficiency and allows family counseling. [1][2]
Broader gene panel or whole-exome sequencing – When the diagnosis is uncertain, broader sequencing can check many immune genes at once and may find other inborn errors that predispose to Kaposi sarcoma or HHV-8 disease. [5][6][24]
Electrodiagnostic tests
Nerve conduction studies and electromyography (EMG) – These tests measure how well nerves and muscles work. [7] They are not routine for this disease but may be used if chemotherapy, antivirals, or other treatments cause possible nerve damage, or if neuropathy symptoms appear. [7][17]
Electrocardiogram (ECG) – An ECG records electrical activity of the heart. [7] It is helpful before and during some treatments (such as certain antivirals or chemotherapy) that may affect heart rhythm, and in patients with anemia or fluid overload from advanced disease. [7]
Non-Pharmacological Treatments
Multidisciplinary rare-disease team care
People with this disorder should be followed in a large hospital or rare-disease center where immunologists, oncologists, hematologists, infectious-disease doctors, and genetic counselors work together.[1] A team like this can plan long-term care, monitor for Kaposi sarcoma and other HHV-8–related problems, and quickly change treatment if new symptoms appear.[1][2] This approach is recommended for many rare immunodeficiencies to improve survival, quality of life, and timely access to clinical trials.[3]Strict infection-prevention and hygiene
Because the immune system is weak, simple infections can become serious, so daily hygiene is very important.[1] This includes regular hand-washing, safe food handling, wearing a mask during outbreaks of viral illness, and avoiding close contact with people who are sick.[2] These basic measures lower exposure to HHV-8 and other viruses and bacteria, and they are widely recommended for patients with primary immunodeficiency and cancer-related immune suppression.[3]Avoiding unnecessary immunosuppressive drugs
Medicines such as long-term steroids, calcineurin inhibitors, or other strong immunosuppressants can further weaken the immune system and may trigger or worsen Kaposi sarcoma in HHV-8–infected people.[1][4] When possible, doctors try to use the lowest effective dose, shortest duration, or safer alternatives, because better immune function reduces the risk of HHV-8–driven tumors.[2][4]Early treatment of infections
Any fever, cough, skin sore, or diarrhea should be checked early by a doctor, because infections can spread quickly in immunodeficient patients.[1] Rapid testing and prompt antibiotics or antivirals can stop minor infections from becoming life-threatening and limit extra immune stress that might allow HHV-8 to reactivate.[2][3] Families are often given an “action plan” telling them when to go to the emergency room.Skin and oral care for Kaposi lesions
People with this disease are at very high risk of childhood-onset Kaposi sarcoma, with purple or brown lesions on the skin and in the mouth.[1][2] Gentle skin care, sun protection, and avoidance of trauma to lesions help prevent bleeding, infection, and pain.[3] Dentists familiar with immunodeficiency can help care for oral lesions and maintain nutrition when mouth sores make eating difficult.[2]Psychological and social support
Chronic rare diseases in childhood can cause fear, sadness, anxiety, and social isolation in both the child and family.[1] Regular psychological support, school counseling, and connection with rare-disease and immunodeficiency patient groups can reduce stress and improve coping.[2][3] Better mental health is also linked with improved treatment adherence and overall outcomes.Nutrition counseling and growth monitoring
Children with chronic infection, cancers, or big spleen may lose weight or fail to grow normally.[1] A dietitian can design high-calorie, high-protein, vitamin-rich meal plans, sometimes using oral nutritional supplements, to support immune cells and tissue repair.[2] Regular weight and height checks allow the team to adjust the plan early if growth slows.Vaccination planning (with specialist guidance)
Vaccines are important but must be carefully planned in combined immunodeficiency.[1] In general, live vaccines (such as some measles or varicella vaccines) may be unsafe, while inactivated vaccines are usually recommended, sometimes with extra doses or antibody checks to ensure protection.[2][4] An immunologist decides which vaccines are safe and when to give them.Household and close-contact vaccination
Even if the patient’s own vaccine response is weak, vaccinating family members and close contacts against common infections creates a “cocoon” of protection around the patient.[1] This strategy lowers the chance that influenza, pneumococcus, or other infections will be brought into the home and passed to the child.[2][3]Education about HHV-8 and Kaposi sarcoma
Families should be taught, in simple language, what HHV-8 is, how it spreads (for example, saliva, sexual contact, blood products), and how Kaposi sarcoma looks.[1][2] Understanding early warning signs helps families seek care quickly if new lesions, swelling, or breathing problems appear, which can make treatment easier and more effective.[3]Safe blood-product use
Some patients need blood transfusions due to anemia or pancytopenia.[1] Hospitals use screened, safe blood products, and in some settings they may consider leukoreduced and pathogen-reduced products to further reduce infectious risks.[2] Careful transfusion practice is a standard part of management in many immunodeficiency and oncology conditions.[3]Physical therapy and activity planning
Fatigue, anemia, or chemotherapy side effects can reduce strength and endurance.[1] A physiotherapist can plan gentle exercises to maintain muscle mass, joint flexibility, and balance, helping the child stay active without over-exertion.[2] Regular movement also supports general health and emotional well-being.Sun-protection strategies
Sun exposure may worsen visible Kaposi lesions and can increase skin-cancer risk, especially when chemotherapy or immunosuppression is used.[1][2] Using hats, long sleeves, and broad-spectrum sunscreen can protect the skin and improve comfort and appearance.[3]Reproductive and genetic counseling for the family
Because this disorder is autosomal recessive, parents and siblings may be carriers.[1] Genetic counseling explains carrier risk, options for prenatal or preimplantation genetic testing, and plans for future pregnancies.[2] This helps families make informed decisions and alerts relatives who might also carry the mutation.[3]School and workplace accommodations
Children may miss school for hospital visits or because of infection risk; adults may struggle to work full-time.[1] Written plans with the school or employer can allow flexible attendance, remote learning or work, and measures to reduce exposure to infections (for example, well-ventilated rooms, mask use during outbreaks).[2][3]Palliative and symptom-control services when needed
In aggressive or advanced disease with organ involvement, palliative-care specialists can help control pain, breathlessness, itching, and other distressing symptoms.[1][2] Early palliative support does not mean stopping active treatment; it is added to improve quality of life for the patient and family.[3]Regular cancer and organ-function surveillance
Because HHV-8 can cause several tumors and lymph-proliferative diseases, regular check-ups with imaging, endoscopy when needed, and laboratory tests help detect problems early.[1][2] Early detection of Kaposi sarcoma, Castleman disease, or lymphoma allows treatment before severe organ damage occurs.[3]Participation in clinical trials and registries
For ultra-rare diseases like this, clinical trials and patient registries help doctors learn which treatments work best.[1] Joining such studies, when available and safe, can give access to novel therapies and improve knowledge for future patients.[2][4]Telemedicine follow-up
Telehealth visits can reduce travel for families who live far from expert centers and lower exposure to infections in hospitals.[1] Regular video appointments help maintain close monitoring, adjust medicines, and quickly discuss new symptoms.[2]Family training in emergency warning signs
Families should learn which signs mean “go to emergency now”, such as high fever, breathing trouble, fast swelling of legs or abdomen, new purple skin lesions, severe bleeding, or confusion.[1] Clear written instructions and an emergency contact number make it easier to act quickly and may save lives.[2]
Drug Treatments
Important: All medicines below must be prescribed and adjusted by specialists. Doses are typical adult examples from FDA labels and cancer guidelines and are not personal medical advice.[1]
Pegylated liposomal doxorubicin (DOXIL – doxorubicin HCl liposome)
This chemotherapy drug is approved for AIDS-related Kaposi sarcoma and is often used for HHV-8–related KS in immunodeficient patients.[1][2] A common dose is about 20 mg/m² intravenously every 2–3 weeks, with adjustments for heart and liver function.[2] It works by damaging cancer-cell DNA, especially in blood-vessel–forming tumor cells, which shrinks Kaposi lesions and improves symptoms.[2][3] Main side effects include low blood counts, mouth sores, nausea, hair loss, heart damage at high cumulative doses, and hand-foot skin reactions.[2]Paclitaxel / Taxol (paclitaxel injection)
Paclitaxel is another chemotherapy agent approved for second-line treatment of AIDS-related Kaposi sarcoma.[1][2] Typical regimens for KS use 100–135 mg/m² by IV infusion every 2–3 weeks, with pre-medication to prevent allergic reactions and dose changes based on white-cell counts.[2] It stops cancer cells by freezing microtubules inside them, blocking cell division.[3] Common side effects are low white cells, hair loss, numbness in hands and feet, nausea, and allergic reactions.[2]Liposomal daunorubicin (DaunoXome)
Liposomal daunorubicin is a chemotherapy drug approved for AIDS-related Kaposi sarcoma and sometimes used when doxorubicin is not suitable.[1] Doses are usually based on body-surface area and given by IV every few weeks in specialized centers.[1][2] Like other anthracyclines, it intercalates into DNA and produces free radicals that kill tumor cells.[2] Side effects include bone-marrow suppression, nausea, hair loss, and possible heart toxicity at high cumulative doses.[2]Interferon alfa-2b (INTRON A)
Interferon alfa-2b is an immune-modulating drug approved for several cancers, including AIDS-related Kaposi sarcoma.[1][2] It is usually given as a subcutaneous injection several times per week at doses such as 30 MIU/m² for KS, but the exact schedule varies and may be lower in children.[2] Interferon boosts anti-viral and anti-tumor immune responses and may slow HHV-8–driven tumor growth.[3] Side effects include flu-like symptoms, fatigue, depression, low blood counts, and liver and thyroid disturbances.[2]Ganciclovir (CYTOVENE-IV, GANZYK-RTU)
Ganciclovir is an antiviral drug that targets herpesviruses and is approved for CMV retinitis in immunocompromised people.[1][2] IV dosing is commonly 5 mg/kg every 12 hours for induction, then a maintenance schedule, adjusted for kidney function.[2] It is not a cure for Kaposi sarcoma, but in some studies anti-herpesvirus drugs reduced HHV-8 viral load and prevented KS in high-risk patients.[3][4] Major side effects are severe neutropenia, anemia, low platelets, kidney problems, and possible carcinogenic and reproductive toxicity.[2]Valganciclovir (VALCYTE)
Valganciclovir is an oral pro-drug of ganciclovir, approved to treat and prevent CMV disease in immunocompromised patients.[1][2] Typical adult dosing for treatment is 900 mg orally twice daily for induction then once daily for maintenance, adjusted for kidney function.[2] It provides ganciclovir exposure similar to IV therapy and may help control HHV-8 replication in some settings, although data in this specific disease are limited.[3][4] Side effects are similar to ganciclovir: bone-marrow suppression, kidney problems, and potential fertility and fetal risks.[2]Rituximab (RITUXAN – rituximab injection)
Rituximab targets CD20-positive B cells and is approved for several lymphomas and autoimmune diseases.[1] It is sometimes used in HHV-8–associated multicentric Castleman disease or lymphoma, which can coexist with Kaposi sarcoma in immunodeficiency.[2][3] A typical dose is 375 mg/m² IV weekly for several weeks, but schedules vary.[1] It works by depleting B cells, which can reduce HHV-8-infected cell populations but may transiently worsen immune suppression.[3] Serious infusion reactions, infections, and rare brain infection (PML) are key risks.[1]Immune globulin intravenous (IVIG – for example ASCENIV, GAMMAGARD LIQUID)
IVIG products are approved for treatment of primary immunodeficiency and provide pooled antibodies from healthy donors.[1][2] Doses for immunodeficiency are typically 400–800 mg/kg IV every 3–4 weeks, adjusted to maintain protective IgG levels.[2] IVIG helps replace missing antibodies, reduces bacterial infections, and may modulate immune responses in autoimmune complications like hemolytic anemia or thrombocytopenia.[1][3] Side effects include headache, infusion reactions, rare kidney injury, and increased blood-clot risk in susceptible patients.[2]Filgrastim (NEUPOGEN – G-CSF)
Filgrastim is a granulocyte colony-stimulating factor that boosts neutrophil production and is approved for neutropenia due to chemotherapy and chronic severe neutropenia.[1][2] Doses often start around 5 µg/kg/day subcutaneously, adjusted according to neutrophil counts.[2][3] In this disease, it can help prevent severe bacterial infections when chemotherapy or bone-marrow failure causes very low neutrophil levels.[3] Common side effects include bone pain, spleen enlargement, and rare splenic rupture or very high white-cell counts.[2]Broad-spectrum antibiotics (for example, trimethoprim-sulfamethoxazole prophylaxis)
Preventive antibiotics are often used in combined immunodeficiency to reduce serious bacterial and Pneumocystis infections.[1] Doses and schedules vary (for example, trimethoprim-sulfamethoxazole once daily or three times weekly), selected by the treating physician.[2] These drugs do not treat HHV-8, but by lowering the burden of other infections they reduce immune stress and hospitalizations.[3] Side effects depend on the specific antibiotic and may include allergic reactions, blood-count changes, or kidney effects.[2]Antifungal prophylaxis (for example, fluconazole when indicated)
In very immunocompromised patients, antifungal drugs may be given to prevent severe fungal infections.[1] Fluconazole doses depend on weight and indication, and must be adjusted in kidney disease.[2] Although not specific to HHV-8, reducing fungal infections is an important part of supportive care in combined T and B cell immunodeficiency.[3] Common side effects include liver-enzyme elevation, nausea, and drug–drug interactions.[2]Prophylactic antivirals for other herpesviruses (for example, acyclovir)
Acyclovir and related drugs are often used to prevent HSV and VZV reactivation in immunocompromised people receiving chemotherapy or steroids.[1] Standard oral doses are used, adjusted for kidney function, according to transplant or oncology protocols.[2] This does not directly target HHV-8 but lowers the overall herpesvirus burden and related complications.[3] Main side effects are kidney problems at high doses or with dehydration and mild gastrointestinal upset.[2]Low-dose aspirin where appropriate
Some experts use low-dose aspirin to reduce clot risk in patients with big spleen, low platelets, or IVIG treatment, but this decision is highly individual.[1] Aspirin works by making platelets less “sticky”, helping to prevent clot formation.[2] However, it can increase bleeding risk, especially in patients with thrombocytopenia or stomach ulcers, so specialists must weigh risks and benefits carefully.[2][3]Proton-pump inhibitors (for example, omeprazole) as stomach protection
Chemotherapy, steroids, and aspirin can irritate the stomach lining.[1] A proton-pump inhibitor reduces stomach acid, which may lower the risk of ulcers and bleeding.[2] Doses and duration depend on the overall treatment plan, and long-term use must be balanced against risks such as infections and nutrient malabsorption.[2][3]Growth-factor support for red cells (erythropoiesis-stimulating agents, when used)
In selected patients with very low red blood cell counts where transfusion alone is not enough, erythropoiesis-stimulating agents may be considered according to oncology and nephrology guidelines.[1] These drugs stimulate the bone marrow to produce more red cells, improving fatigue and exercise tolerance.[2] They carry risks of high blood pressure and thrombosis and must be used with strict monitoring.[2][3]Analgesics and anti-itch medicines
Pain from lesions, nerve damage, or procedures is treated with step-wise pain medicines, starting from simple drugs like paracetamol and going up to stronger agents if needed.[1] Antihistamines or other anti-itch drugs may be used when skin lesions cause intense itching.[2] Correct dosing and monitoring are essential, especially if liver or kidney function is impaired.[2][3]Antiemetics during chemotherapy
Drugs such as ondansetron are often used to prevent nausea and vomiting caused by anthracyclines and paclitaxel.[1] Taken before and sometimes after chemotherapy, they block serotonin receptors in the gut and brain, making treatment easier to tolerate and helping maintain nutrition.[2] Side effects are usually mild but may include constipation, headache, or rare heart-rhythm changes.[2][3]Topical treatments for small Kaposi lesions (for example, topical retinoids or cryotherapy)
In selected cases, small localized skin lesions may be treated with local agents like topical alitretinoin or with freezing (cryotherapy), based on Kaposi sarcoma practice.[1][2] These approaches can improve cosmetic appearance and symptom control, but they do not replace systemic treatment when disease is widespread.[2][3]Corticosteroids (short, carefully controlled courses)
Steroids may sometimes be needed for autoimmune complications, such as hemolytic anemia or platelet destruction, but they can also worsen Kaposi sarcoma if over-used.[1][2] Therefore, they are usually given at the lowest effective dose for the shortest possible time, under close oncologic and immunologic supervision.[2] Side effects include weight gain, infection risk, high blood pressure, bone loss, and mood changes.[2][3]Tailored combination regimens
In practice, doctors often combine several of the medicines above—such as liposomal anthracycline plus antivirals plus IVIG—based on the patient’s age, organ function, and tumor burden.[1][2] There is no “one-size-fits-all” protocol, and treatment may change over time as new evidence appears or new complications arise.[3][4]
Dietary Molecular Supplements
Always discuss supplements with the specialist team to avoid drug interactions and overdose.
Vitamin D
Vitamin D helps immune cells recognize and respond to infections and supports bone health.[1] In deficiency, doctors may prescribe daily or weekly doses (for example, 600–2000 IU/day in children or adults), adjusted by blood levels.[2] Correcting low vitamin D may improve general immune function, muscle strength, and mood, but very high doses can cause high calcium and kidney damage.[2][3]Omega-3 fatty acids (fish-oil–derived)
Omega-3 fatty acids have anti-inflammatory properties and may help reduce chronic inflammation linked to cancer and infections.[1] Typical supplemental doses range from 500–2000 mg/day of EPA/DHA, depending on age and co-morbidities.[2] They may support heart health and modulate immune responses, but high doses can increase bleeding risk, especially with low platelets or aspirin use.[2][3]Zinc
Zinc is essential for normal T-cell development and function.[1] When deficiency is documented, low-dose supplements (for example, 5–20 mg elemental zinc/day depending on age) may be used for a limited period.[2] Too much zinc can actually weaken immunity and cause copper deficiency, so dosing and duration must be carefully controlled.[2][3]Vitamin C
Vitamin C supports white-blood-cell function and acts as an antioxidant.[1] Many patients meet their needs through diet, but some may receive modest supplements like 100–500 mg/day, especially during infection or chemotherapy, if not contraindicated.[2] Very high doses can cause diarrhea and kidney stones, especially in people with kidney problems.[2][3]Folate (folic acid) and vitamin B12
Folate and B12 are required for DNA synthesis in bone marrow, which is critical for blood-cell production.[1] If laboratory tests show deficiency, doctors prescribe appropriate oral or injectable doses (for example, 400 µg/day folic acid, or B12 injections) until stores normalize.[2] Correcting these deficiencies can improve anemia and overall energy, but unnecessary high doses offer no benefit and may mask other problems.[2][3]Iron (only when iron-deficiency anemia is proven)
Iron supplements can raise hemoglobin when iron stores are low, but they should only be used after tests confirm deficiency, because iron overload can be dangerous.[1] Doses and duration depend on age and severity of anemia.[2] Proper iron therapy improves oxygen delivery and reduces fatigue, which indirectly supports immune health.[2][3]High-protein peptide formulas or powders
Some patients with poor appetite or mouth lesions may benefit from medical-grade high-protein formulas.[1] These products provide amino acids needed to build immune cells, antibodies, and repair tissues.[2] Dietitians tailor the dose (for example, number of servings per day) to calorie and protein needs and monitor weight and kidney function.[2][3]Glutamine (when recommended by oncology team)
Glutamine is an amino acid used by rapidly dividing cells, including immune and intestinal cells.[1] Some oncology protocols use short-term glutamine to reduce mouth sores, but evidence is mixed and dosing varies.[2] It should only be used under specialist guidance, because in some cancers high glutamine availability might theoretically support tumor growth.[2][3]Probiotic preparations (carefully selected)
Probiotics may help maintain gut-microbiome balance and reduce antibiotic-associated diarrhea in some patients.[1] However, in very immunocompromised individuals they can rarely cause bloodstream infections, so strains and doses must be chosen by specialists.[2] When used safely, they may support gut health and possibly modulate immune responses.[2][3]Multivitamin/mineral appropriate for age
A simple age-appropriate multivitamin/mineral supplement can help fill mild dietary gaps, especially when appetite is reduced.[1] It is usually taken once daily at the recommended dose to avoid vitamin toxicity.[2] Supplements are an addition, not a substitute, for a balanced diet rich in natural foods.[2][3]
Immunity-Booster, Regenerative and Stem-Cell–Related Drugs
Immune globulin (IVIG/SCIG) as long-term immune replacement
Regular IVIG or subcutaneous immunoglobulin (SCIG) is one of the most important “immune-booster” treatments for many primary immunodeficiencies.[1][2] It does not fix the genetic defect but supplies ready-made antibodies, lowering serious bacterial infections and sometimes stabilizing autoimmune problems.[2] Dose and route are individualized and adjusted based on IgG levels and infection history.[2][3]Filgrastim (G-CSF) for neutrophil regeneration
As noted above, filgrastim can be seen as a regenerative growth factor for neutrophils.[1] It stimulates bone-marrow stem cells to produce and release neutrophils into the blood, reducing the length and severity of neutropenia.[2] Careful monitoring prevents extreme leukocytosis and detects spleen enlargement early.[2][3]Erythropoiesis-stimulating agents for red-cell support
In selected cases with chronic anemia due to bone-marrow failure or chemotherapy, erythropoiesis-stimulating agents may help the marrow regenerate red cells.[1] They act on early red-cell precursors to increase red-cell production, but carry risks of high blood pressure and clots.[2] They are usually used for clear indications and limited periods, with strict lab monitoring.[2][3]mTOR-targeting drugs (for example, sirolimus in selected HHV-8–related conditions)
Sirolimus is an mTOR inhibitor approved for transplant immunosuppression, but it also has anti-angiogenic and anti-tumor properties and has been explored in some Kaposi sarcoma and vascular-tumor settings.[1][2] In this very rare disease, use would be highly experimental and carefully balanced against the risk of further immunosuppression.[2][3] Doses and side effects (mouth ulcers, high lipids, infection risk) follow transplant oncology experience.[2]Experimental targeted or monoclonal antibody therapies
As researchers better understand how HHV-8 interacts with immune and signaling pathways, new targeted drugs and monoclonal antibodies may be tested in trials.[1] These agents aim to selectively block tumor-promoting signals or enhance anti-viral immunity while sparing healthy tissues.[2] Because evidence is still emerging, such treatments are used only in clinical trials or highly specialized centers.[2][3]Hematopoietic stem cell transplantation (HSCT – see also surgeries)
Allogeneic HSCT can replace the patient’s faulty immune system with donor stem cells and may offer the only potential “cure” for some combined immunodeficiencies.[1] Conditioning regimens, donor selection, and timing are complex and must weigh transplant risks (such as graft-versus-host disease and infections) against the severity of Kaposi sarcoma and other complications.[2][3] Evidence for this specific HHV-8-related disorder is limited to case reports and expert opinion.[2]
Surgeries and Procedures
Diagnostic and staging biopsies
Skin or lymph-node biopsies are often needed to confirm Kaposi sarcoma or other HHV-8–related tumors.[1] Under local or general anesthesia, a surgeon removes a small piece of tissue for microscopic and virologic analysis.[2] This guides treatment choices by showing how aggressive the tumor is and whether other diseases like lymphoma or Castleman disease are present.[2][3]Local excision of isolated lesions
When there are only a few problematic skin or mucosal lesions (for example, causing bleeding, pain, or obstruction), surgeons may remove them.[1] Excision can improve function and appearance in selected areas, but new lesions can still appear elsewhere, so it is not a full cure.[2]Endoscopic procedures for internal lesions
If lesions affect the gut or airways, endoscopy (camera inside the bowel or lungs) allows biopsies, local treatments such as cauterization, and assessment of bleeding or obstruction.[1][2] These procedures help diagnose complications early and sometimes prevent emergency surgery.[2][3]Splenectomy (rare, highly selected cases)
In some patients with massive splenomegaly causing pain, severe anemia, or platelets being trapped in the spleen, splenectomy may be considered.[1] Removing the spleen can improve blood counts but increases lifelong infection risk, so vaccines and antibiotic prophylaxis become even more important.[2][3]Hematopoietic stem cell transplantation (HSCT) procedures
HSCT involves multiple surgical or interventional steps, including central-line placement, bone-marrow harvest from donor hips, and infusion of stem cells into the recipient.[1] The goal is to rebuild the immune system with healthy donor cells, which may reduce susceptibility to HHV-8–related disease over time.[2] HSCT carries significant risks and is considered only after careful evaluation at specialized centers.[2][3]
Preventions
Genetic counseling and carrier testing before future pregnancies[1]
Early diagnosis and regular follow-up at a rare-disease or immunology center[1][2]
Strict hand hygiene, safe food, and avoidance of sick contacts to limit infections[3]
Avoiding unnecessary immunosuppressive drugs and carefully managing any needed steroids[4]
Safe blood-product use and screening according to national standards[3]
Vaccination of household members and appropriate inactivated vaccines for the patient[1][2]
Education on safe sexual practices in adolescents and adults to reduce HHV-8 transmission[3][4]
Rapid medical review of any new skin, mouth, or lymph-node lesions[2]
Healthy lifestyle: good sleep, balanced diet, and avoidance of smoking and alcohol[3]
Participation in registries and clinical trials to improve knowledge and future prevention strategies[1][4]
When to See Doctors
People with combined immunodeficiency and HHV-8 susceptibility should be in regular contact with an immunologist and oncologist, not only when problems appear.[1] They should seek urgent medical care if there is high fever, rapid breathing, severe cough, new or rapidly spreading purple or brown skin spots, swelling of legs or abdomen, bleeding, severe headache, confusion, or sudden weight loss.[2][3] Even minor symptoms can progress quickly in this disease, so families are usually told to act early and not wait at home.[3][4]
What to Eat and What to Avoid
Eat a diet rich in natural foods: fruits, vegetables, whole grains, beans, and lean proteins like fish, eggs, and poultry to support immune and tissue repair.[1]
Eat enough calories and protein; small, frequent meals or nutritional drinks can help when appetite is low.[2]
Eat safe, well-cooked foods; avoid undercooked meat, raw eggs, and unpasteurized milk to reduce infection risk.[3]
Eat iron-, folate-, and B12-rich foods (green leafy vegetables, beans, meat, fortified cereals) when not medically restricted, to support blood formation.[2][3]
Avoid raw or unwashed fruits and vegetables in settings where food safety is poor or neutrophil counts are very low.[3]
Avoid excessive sugar-sweetened drinks and ultra-processed snacks, which add calories but few nutrients and may worsen weight gain or metabolic issues.[2]
Avoid alcohol and smoking; they damage organs and further weaken immunity and healing.[3]
Avoid herbal supplements or “immune boosters” without specialist review, because they may interact with chemotherapy or antivirals.[1][4]
Ensure safe drinking water (treated or boiled where needed) to prevent gut infections.[3]
Check all nutrition plans with the medical team, especially during chemotherapy or HSCT, when special diet rules may apply.[2][4]
Frequently Asked Questions
Is this disease the same as “ordinary” Kaposi sarcoma?
No. Kaposi sarcoma is the tumor caused by HHV-8, but this rare condition is a genetic immune-system disease that makes Kaposi sarcoma much more likely and often more aggressive in childhood.[1][2]Is combined immunodeficiency with impaired immunity to HHV-8 inherited?
Yes. It is usually autosomal recessive, meaning a child gets one faulty gene from each parent.[1] Parents are typically healthy carriers; siblings may also be carriers or, rarely, affected.[1][3]Can this condition be cured?
Most standard treatments control symptoms, prevent infections, and treat tumors but do not fix the underlying gene problem.[1] In some patients, allogeneic stem cell transplantation may offer a potential cure, but it carries serious risks and is not yet well-studied in this exact disease.[2][3]What is the role of HHV-8 in this disease?
HHV-8 is the virus that causes Kaposi sarcoma and some lymph-proliferative diseases.[2][4] In this combined immunodeficiency, the body cannot control HHV-8 well, so the virus can more easily drive tumor formation and chronic inflammation.[2]Are anti-HHV-8 antivirals enough to control the disease?
Antivirals like ganciclovir and valganciclovir can reduce HHV-8 replication and may help prevent KS in some settings, but once tumors are established, chemotherapy and immune-modulating treatments are usually needed.[2][4]Why are chemotherapy drugs used in a child with an immune problem?
Kaposi sarcoma and related tumors are life-threatening if not treated.[2][3] Carefully chosen chemotherapy (such as liposomal anthracyclines or paclitaxel) can shrink tumors and improve survival, while the medical team uses supportive care like IVIG and growth factors to protect the immune system as much as possible.[2]Can regular vaccines still be given?
Some inactivated vaccines are usually recommended, but live vaccines may be unsafe.[1][4] An immunologist should design a personal vaccine plan and decide which vaccines are safe for the child and when to give them.How is this disease diagnosed?
Diagnosis involves detailed clinical history, blood tests for immune-cell counts and function, tests for HHV-8 and Kaposi sarcoma, and genetic testing to identify pathogenic variants such as OX40 (TNFRSF4) mutations.[1][2]Can a person with this disease live a long life?
Outcomes vary widely.[1] With early diagnosis, expert care, aggressive infection-prevention, and proper treatment of tumors and blood problems, many complications can be managed, but the disease is serious and needs lifelong follow-up.[1][3]Is it safe for patients to attend school or work?
Often yes, with proper precautions.[2] Plans may include avoiding contact with sick people, extra hygiene, mask use during outbreaks, and flexibility for medical appointments and periods of low counts.[2][3]What are the biggest dangers to watch for at home?
The major dangers are severe infections, rapid growth or spread of Kaposi lesions, breathing problems, severe bleeding, and sudden changes in behavior or consciousness.[2][3][4] Families should have written emergency instructions from their care team.Can diet alone fix the immune defect?
No. Healthy food and supplements can support general health and help the body cope with treatment, but they cannot correct the genetic immune problem.[1][2] Medical treatments and regular follow-up remain essential.Are alternative medicines recommended?
There is no strong evidence that unproven alternative therapies cure this disease or Kaposi sarcoma, and some may be harmful or interact with chemotherapy or antivirals.[2][4] All non-prescription products should be discussed with the medical team before use.Should family members be tested?
Yes, genetic counseling and testing are usually recommended for parents and siblings to identify carriers and possibly detect other affected family members early.[1][3] Early detection allows faster preventive care and monitoring.Where can families find more information and support?
Families can seek information from national rare-disease and primary immunodeficiency organizations and from large academic centers that run immunology, oncology, or HSCT programs.[1][2] These groups provide educational materials, access to experts, and community support.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: February 14, 2025.
